Novel use of an irrigated ablation catheter to monitor real-time hemodynamics during ablation.

INTRODUCTION: Hemodynamic decompensation during catheter ablation occurs due to prolonged procedure time and irrigant delivery directly into the cardiac chambers. Real-time hemodynamic monitoring of patients undergoing catheter ablation procedures may identify patients at risk of decompensation; we set out to assess the feasibility of a novel, real-time, intracardiac pressure monitoring system using a standard irrigated ablation catheter. METHODS: We studied 13 consecutive who underwent pressure measurement of the left atrium (LA) and left ventricle (LV) via transeptal access with a Swan Ganz (SG) catheter followed by two commercially available irrigated ablation catheters. Pressure waveform data was extracted to compare LA peak pressure, LV peak systolic pressure, LV end-diastolic pressure, and waveform analysis. RESULTS: Comparison between the SG and ablation catheters (AblA; AblB) demonstrated that LV systolic pressure (0.61-16.8 mmHg; 1.32-18.2 mmHg), and LV end-diastolic pressure (-3.4 to 2.8 mmHg; -3.0 to 3.35 mmHg) were well correlated and had accepted repeatability. Ablation waveforms demonstrated an 89.9 ± 6.4% correlation compared to SG waveforms. CONCLUSION: Pressure measurements derived from an irrigated ablation catheter are accurate and reliable when compared to an SG catheter. Further studies are needed to determine how real-time pressure monitoring can improve outcomes during ablation procedures.

Complex repolarization dynamics in ex vivo human ventricles are independent of the restitution properties.

AIMS: The mechanisms of transition from regular rhythms to ventricular fibrillation (VF) are poorly understood. The concordant to discordant repolarization alternans pathway is extensively studied; however, despite its theoretical centrality, cannot guide ablation. We hypothesize that complex repolarization dynamics, i.e. oscillations in the repolarization phase of action potentials with periods over two of classic alternans, is a marker of electrically unstable substrate, and ablation of these areas has a stabilizing effect and may reduce the risk of VF. To prove the existence of higher-order periodicities in human hearts. METHODS AND RESULTS: We performed optical mapping of explanted human hearts obtained from recipients of heart transplantation at the time of surgery. Signals recorded from the right ventricle endocardial surface were processed to detect global and local repolarization dynamics during rapid pacing. A statistically significant global 1:4 peak was seen in three of six hearts. Local (pixel-wise) analysis revealed the spatially heterogeneous distribution of Periods 4, 6, and 8, with the regional presence of periods greater than two in all the hearts. There was no significant correlation between the underlying restitution properties and the period of each pixel. CONCLUSION: We present evidence of complex higher-order periodicities and the co-existence of such regions with stable non-chaotic areas in ex vivo human hearts. We infer that the oscillation of the calcium cycling machinery is the primary mechanism of higher-order dynamics. These higher-order regions may act as niduses of instability and may provide targets for substrate-based ablation of VF.

Hands-on defibrillation with safety drapes: Analysis of compressions and an alternate current pathway.

BACKGROUND: Hands-on defibrillation (HOD) could theoretically improve the efficacy of cardiopulmonary resuscitation (CPR) though a few mechanisms. Polyethylene drapes could potentially facilitate safe HOD, but questions remain about the effects of CPR on polyethylene's conductance and the magnitude of current looping through rescuers' arms in contact with patients. METHODS: This study measured the leakage current through 2 mil (0.002 in.) polyethylene through two different current pathways before and after 30 min of continuous compressions on a CPR mannequin. The two pathways analyzed were the standardized IEC (International Electrotechnical Commission) leakage current analysis and a setup analyzing a current pathway looping through a rescuer's arms and returning to the patient. First, ten measurements involving the two pathways were obtained on a single polyethylene drape. 30 min of continuous compressions were applied to the drape on a CPR mannequin after which the ten measurements were repeated. RESULTS: Twenty patients undergoing elective cardioversion for atrial fibrillation (18/20) or atrial flutter (2/20) at Emory University Hospital underwent analysis all receiving 200 J shocks (age 38-101, 35% female). Through the IEC measurement method the peak leakage current mean was 0.70 +/- 0.02 mA before compressions and 0.59 +/- 0.19 mA after compressions. Only three of the ten measurements assessing current passing through a rescuer's arms had detectable current and each was of low magnitude. All measurements were well below the maximum IEC recommendations of 3.5 mA RMS and 5.0 mA peak. CONCLUSIONS: Polyethylene may facilitate safe HOD even after long durations of compressions. Current looping through a rescuer's arms is likely of insignificant magnitude.

Experience using multielectrode cardiac catheters for detection of electrophysiologic activity of the human urinary bladder.

AIM: To determine the feasibility of commercially available multielectrode cardiac electrophysiology catheters to detect electrical activity in the human bladder. METHODS: Ten subjects requiring cystoscopy for the evaluation of lower urinary tract pathology were eligible for participation in our study. After routine rigid cystoscopy with a 70° cystoscope, various multielectrode cardiac electrophysiology catheters were introduced into the bladder. One of three catheters with different electrode configurations was used per subject. Electroanatomical images of the bladder were created and spontaneous electrical activity was recorded. Subjective response to electrical stimuli delivered across the electrodes (20 mA at 5 ms pulse width, rate 100 ms) was also recorded. The responses were qualitatively compared with that from a prior study. RESULTS: Electrical activity recorded at the dome of the bladder was less than 0.5 mV and low frequency. Myopotentials resembling smooth muscle were detected at electrodes near or within the trigone. A sensory response was reported with the use of pacing stimuli, with the sensation in the trigone being reported more often than the dome of the bladder. Stimulation in the trigone triggered sensory urgency and voiding in a patient with a history of overactive bladder. CONCLUSIONS: The use of multielectrode catheters to measure human bladder electrophysiologic activity is feasible. Issues with noise reduction still exist, though to a lesser extent with the multielectrode basket design than simple quadripolar one. Sensory responses to pacing stimuli may be useful for diagnostic and therapeutic purposes in the future.

Generation of Monophasic Action Potentials and Intermediate Forms.

The monophasic action potential (MAP) is a near replica of the transmembrane potential recorded when an electrode is pushed firmly against cardiac tissue. Despite its many practical uses, the mechanism of MAP signal generation and the reason it is so different from unipolar recordings are not completely known and are a matter of controversy. In this work, we describe a method to simulate realistic MAP and intermediate forms, which are multiphasic electrograms different from an ideal MAP. The key ideas of our method are the formation of compressed zones and junctional spaces-regions of the extracellular and bath or blood pool directly in contact with electrodes that exhibit a pressure-induced reduction in electrical conductivity-and the presence of a complex network of passive components that acts as a high-pass filter to distort and attenuate the signal that reaches the recording amplifier. The network is formed by the interaction between the passive tissue properties and the double-layer capacitance of electrodes. The MAP and intermediate forms reside on a continuum of signals, which can be generated by the change of the model parameters. Our model helps to decipher the mechanisms of signal generation and can lead to a better design for electrodes, recording amplifiers, and experimental setups.

Critical phase transitions during ablation of atrial fibrillation.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia with significant morbidity and mortality. Pharmacological agents are not very effective in the management of AF. Therefore, ablation procedures have become the mainstay of AF management. The irregular and seemingly chaotic atrial activity in AF is caused by one or more meandering spiral waves. Previously, we have shown the presence of sudden rhythm organization during ablation of persistent AF. We hypothesize that the observed transitions from a disorganized to an organized rhythm is a critical phase transition. Here, we explore this hypothesis by simulating ablation in an anatomically-correct 3D AF model. In 722 out of 2160 simulated ablation, at least one sudden transition from AF to an organized rhythm (flutter) was noted (33%). They were marked by a sudden decrease in the cycle length entropy and increase in the mean cycle length. At the same time, the number of reentrant wavelets decreased from 2.99 ± 0.06 in AF to 1.76 ± 0.05 during flutter, and the correlation length scale increased from 13.3 ± 1.0 mm to 196.5 ± 86.6 mm (both P < 0.0001). These findings are consistent with the hypothesis that transitions from AF to an anatomical flutter behave as phase transitions in complex non-equilibrium dynamical systems with flutter acting as an absorbing state. Clinically, the facilitation of phase transition should be considered a novel mechanism of ablation and may help to design effective ablation strategies.

Relationship between mechanical dyssynchrony and intra-operative electrical delay times in patients undergoing cardiac resynchronization therapy.

BACKGROUND: It is important to understand the relationship between electrical and mechanical ventricular activation in CRT patients. By measuring local electrical activation at multiple locations within the coronary veins and myocardial contraction at the same locations in the left ventricle, we determined the relationship between electrical and mechanical activation at potential left ventricular pacing locations. METHODS: In this study, mechanical contraction times were computed using high temporal resolution cine cardiovascular magnetic resonance (CMR) data, while electrical activation times were derived from intra-procedural local electrograms. RESULTS: In our cohort, there was a strong correlation between electrical and mechanical delay times within each patient (R2=0.78 ± 0.23). Additionally, the latest electrically activated location corresponded with the latest mechanically contracting location in 91% of patients. CONCLUSIONS: This study provides initial evidence that our method of obtaining non-invasive mechanical activation patterns accurately reflects the underlying electromechanical substrate of intraventricular dyssynchrony.

Accurate detection of lead malfunction from ECG-derived bipolar pacing stimulus amplitude.

BACKGROUND: One common mode of lead failure is insulation breach, which may result in myopotential noise and device malfunction. "Pseudo-unipolarization" of bipolar pacing stimuli, as observed from a routine 12-lead electrocardiogram (ECG) due to stimulus current leak, has been observed with insulation breaches. OBJECTIVE: We sought to characterize this electrocardiographic finding to detect this type of lead malfunction. METHODS: A total of 138 transvenous leads were analyzed, including 88 with known malfunction and 50 normal leads. The amplitude of a bipolar pacing stimulus on the ECG was recorded and compared with a control data set of newly implanted leads with bipolar stimuli normalized for output. RESULTS: The malfunction group consisted of 61% right atrium and 39% right ventricle leads with mean pacing output of 2.74 V at 0.5 ms. There was a significant difference in ECG bipolar stimulus amplitudes at time of identification of failure (7.89 ± 7.56 mm/V; P < .001) compared with those of normal leads (0.86 ± 0.41 mm/V). Receiver operating characteristic curve for the prediction of lead malfunction based on absolute ECG amplitude displayed an area under the curve of 0.93 (95% CI, 0.891-0.969). When normalized for programmed stimulus output, a cutoff of 5 mm/V demonstrated a sensitivity of 91% and a specificity of 92% (area under the curve, 0.967; 95% CI, 0.938-0.996). CONCLUSION: The maximum amplitude of a bipolar pacing stimulus on the ECG is significantly lower in normal functioning leads compared with those with known malfunction. This simply derived variable demonstrated good accuracy at identifying lead failure due to insulation breach.

A cross species thermoelectric and spatiotemporal analysis of alternans in live explanted hearts using dual voltage-calcium fluorescence optical mapping.

Objective.Temperature plays a crucial role in influencing the spatiotemporal dynamics of the heart. Electrical instabilities due to specific thermal conditions typically lead to early period-doubling bifurcations and beat-to-beat alternans. These pro-arrhythmic phenomena manifest in voltage and calcium traces, resulting in compromised contractile behaviors. In such intricate scenario, dual optical mapping technique was used to uncover unexplored multi-scale and nonlinear couplings, essential for early detection and understanding of cardiac arrhythmia.Approach.We propose a methodological analysis of synchronized voltage-calcium signals for detecting alternans, restitution curves, and spatiotemporal alternans patterns under different thermal conditions, based on integral features calculation. To validate our approach, we conducted a cross-species investigation involving rabbit and guinea pig epicardial ventricular surfaces and human endocardial tissue under pacing-down protocols.Main results.We show that the proposed integral feature, as the area under the curve, could be an easily applicable indicator that may enhance the predictability of the onset and progression of cardiac alternans. Insights into spatiotemporal correlation analysis of characteristic spatial lengths across different heart species were further provided.Significance.Exploring cross-species thermoelectric features contributes to understanding temperature-dependent proarrhythmic regimes and their implications on coupled spatiotemporal voltage-calcium dynamics. The findings provide preliminary insights and potential strategies for enhancing arrhythmia detection and treatment.

Beyond Alternans: Detection of Higher-Order Periodicity in Ex-Vivo Human Ventricles Before Induction of Ventricular Fibrillation.

Background: Repolarization alternans, defined as period-2 oscillation in the repolarization phase of the action potentials, is one of the cornerstones of cardiac electrophysiology as it provides a mechanistic link between cellular dynamics and ventricular fibrillation (VF). Theoretically, higher-order periodicities (e.g., period-4, period-8,...) are expected but have very limited experimental evidence. Methods: We studied explanted human hearts, obtained from the recipients of heart transplantation at the time of surgery, using optical mapping technique with transmembrane voltage-sensitive fluorescent dyes. The hearts were stimulated at an increasing rate until VF was induced. The signals recorded from the right ventricle endocardial surface just before the induction of VF and in the presence of 1:1 conduction were processed using the Principal Component Analysis and a combinatorial algorithm to detect and quantify higher-order dynamics. Results: A prominent and statistically significant 1:4 peak (corresponding to period-4 dynamics) was seen in three of the six studied hearts. Local analysis revealed the spatiotemporal distribution of higher-order periods. Period-4 was localized to temporally stable islands. Higher-order oscillations (period-5, 6, and 8) were transient and primarily occurred in arcs parallel to the activation isochrones. Discussion: We present evidence of higher-order periodicities and the co-existence of such regions with stable non-chaotic areas in ex-vivo human hearts before VF induction. This result is consistent with the period-doubling route to chaos as a possible mechanism of VF initiation, which complements the concordant to discordant alternans mechanism. The presence of higher-order regions may act as niduses of instability that can degenerate into chaotic fibrillation.

Higher-Order Dynamics Beyond Repolarization Alternans in Ex-Vivo Human Ventricles are Independent of the Restitution Properties.

Background: Repolarization alternans, defined as period-2 oscillation in the repolarization phase of the action potentials, provides a mechanistic link between cellular dynamics and ventricular fibrillation (VF). Theoretically, higher-order periodicities (e.g., periods 4, 6, 8,...) are expected but have minimal experimental evidence. Methods: We studied explanted human hearts obtained from recipients of heart transplantation at the time of surgery. Optical mapping of the transmembrane potential was performed after staining the hearts with voltage-sensitive fluorescent dyes. Hearts were stimulated at an increasing rate until VF was induced. Signals recorded from the right ventricle endocardial surface prior to induction of VF and in the presence of 1:1 conduction were processed using the Principal Component Analysis and a combinatorial algorithm to detect and quantify higher-order dynamics. Results were correlated to the underlying electrophysiological characteristics as quantified by restitution curves and conduction velocity. Results: A prominent and statistically significant global 1:4 peak (corresponding to period-4 dynamics) was seen in three of the six studied hearts. Local (pixel-wise) analysis revealed the spatially heterogeneous distribution of periods 4, 6, and 8, with the regional presence of periods greater than two in all the hearts. There was no significant correlation between the underlying restitution properties and the period of each pixel. Discussion: We present evidence of higher-order periodicities and the co-existence of such regions with stable non-chaotic areas in ex-vivo human hearts. We infer from the independence of the period to the underlying restitution properties that the oscillation of the excitation-contraction coupling and calcium cycling mechanisms is the primary mechanism of higher-order dynamics. These higher-order regions may act as niduses of instability that can degenerate into chaotic fibrillation and may provide targets for substrate-based ablation of VF.

Left atrial flutter accelerates during ablation of atrial fibrillation: a paradoxical effect of electrical remodelling.

AIMS: Atrial fibrillation (AF)-induced electrical remodelling causes shortening of refractory period and slowing of conduction velocity. During the course of catheter ablation of AF, there are often transitions from AF to left atrial flutter (AFL) and from faster to slower AFL. The purpose of this study was to characterize the time course of change in AFL rate during AF ablation. METHODS AND RESULTS: Fourier transformation was performed on 16 s segments of coronary sinus and ablation catheter bipolar electrograms. Ablation-induced AF-to-AFL and AFL-to-AFL transitions were defined as a sudden drop in the dominant frequency (DF) of at least 10 bpm, followed by a regular rhythm. Forty-five transitions were detected in 24 ablation procedures. The mean DF in AF was 5.31 ± 0.79 Hz, which was significantly faster than AFL, 4.52 ± 0.62 Hz (P< 0.05). The mean ΔDF at transitions was -51 ± 16 bpm in AF and -40 ± 14 bpm in AFL. Dominant frequency slope was positive (rate increased) after all the transitions during AF (P< 0.0001) and in 11 of 14 transitions in AFL (P= 0.033). The time constant of the DF recovery curve was 161 ± 105 s. CONCLUSIONS: After ablation-induced transition from AF to AFL, or faster to slower AFL, there is a progressive increase in AFL rate over time. The mechanism of this acceleration is uncertain, but the time constant of this rate increase is consistent with the recovery of the slow/ultraslow sodium current in the setting of established electrical remodelling.

Methodology for Cross-Talk Elimination in Simultaneous Voltage and Calcium Optical Mapping Measurements With Semasbestic Wavelengths.

Most cardiac arrhythmias at the whole heart level result from alteration of cell membrane ionic channels and intracellular calcium concentration ([Ca2+] i ) cycling with emerging spatiotemporal behavior through tissue-level coupling. For example, dynamically induced spatial dispersion of action potential duration, QT prolongation, and alternans are clinical markers for arrhythmia susceptibility in regular and heart-failure patients that originate due to changes of the transmembrane voltage (V m) and [Ca2+] i . We present an optical-mapping methodology that permits simultaneous measurements of the V m - [Ca2+] i signals using a single-camera without cross-talk, allowing quantitative characterization of favorable/adverse cell and tissue dynamical effects occurring from remodeling and/or drugs in heart failure. We demonstrate theoretically and experimentally in six different species the existence of a family of excitation wavelengths, we termed semasbestic, that give no change in signal for one dye, and thus can be used to record signals from another dye, guaranteeing zero cross-talk.

Circle Method for Robust Estimation of Local Conduction Velocity High-Density Maps From Optical Mapping Data: Characterization of Radiofrequency Ablation Sites.

Conduction velocity (CV) slowing is associated with atrial fibrillation (AF) and reentrant ventricular tachycardia (VT). Clinical electroanatomical mapping systems used to localize AF or VT sources as ablation targets remain limited by the number of measuring electrodes and signal processing methods to generate high-density local activation time (LAT) and CV maps of heterogeneous atrial or trabeculated ventricular endocardium. The morphology and amplitude of bipolar electrograms depend on the direction of propagating electrical wavefront, making identification of low-amplitude signal sources commonly associated with fibrotic area difficulty. In comparison, unipolar electrograms are not sensitive to wavefront direction, but measurements are susceptible to distal activity. This study proposes a method for local CV calculation from optical mapping measurements, termed the circle method (CM). The local CV is obtained as a weighted sum of CV values calculated along different chords spanning a circle of predefined radius centered at a CV measurement location. As a distinct maximum in LAT differences is along the chord normal to the propagating wavefront, the method is adaptive to the propagating wavefront direction changes, suitable for electrical conductivity characterization of heterogeneous myocardium. In numerical simulations, CM was validated characterizing modeled ablated areas as zones of distinct CV slowing. Experimentally, CM was used to characterize lesions created by radiofrequency ablation (RFA) on isolated hearts of rats, guinea pig, and explanted human hearts. To infer the depth of RFA-created lesions, excitation light bands of different penetration depths were used, and a beat-to-beat CV difference analysis was performed to identify CV alternans. Despite being limited to laboratory research, studies based on CM with optical mapping may lead to new translational insights into better-guided ablation therapies.

A Network-based Cardiac Electrophysiology Simulator with Realistic Signal Generation and Response to Pacing Maneuvers.

Diagnosis and localization of cardiac arrhythmias, especially supraventricular tachycardia (SVT), by inspecting intracardiac signals and performing pacing maneuvers is the core of electrophysiology studies. Acquiring and maintaining complex skill sets can be facilitated by using simulators, allowing the operator to practice in a safe and controlled setting. An electrophysiology simulator should not only display arrhythmias but it has to respond to the user's arbitrary inputs. While, in principle, it is possible to model the heart using a detailed anatomical and cellular model, such a system would be unduly complex and computationally intensive. In this paper, we describe a freely available web-based electrophysiology simulator (http://svtsim.com), which is composed of a visualization/interface unit and a heart model based on a dynamical network. In the network, nodes represent the points of interest, such as the sinus and the atrioventricular nodes, and links model the conduction system and pathways. The dynamics are encoded explicitly in the state machines attached to the nodes and links. Simulated intracardiac signals and surface ECGs are generated from the internal state of the heart model. Reentrant tachycardias, especially various forms of SVT, can emerge in this system in response to the user's actions in the form of pacing maneuvers. Additionally, the resulting arrhythmias respond realistically to various inputs, such as overdrive pacing and delivery of extra stimuli, cardioversion, ablation, and infusion of medications. For nearly a decade, svtsim.com has been used successfully to train electrophysiology practitioners in many institutions. We will present our experience regarding best practices in designing and using electrophysiology simulators for training and testing. We will also discuss the current trends in clinical cardiac electrophysiology and the anticipated next generation electrophysiology simulators.

Not all Long-QTs Are The Same, Proarrhytmic Quantification with Action Potential Triangulation and Alternans.

Long-QT is commonly associated with an increased risk of polymorphic ventricular tachycardia from drug therapy. However, not all drugs prolonging QT interval are proarrhythmic. This study aimed to characterize cellular and tissue mechanisms under which QT-interval prolonging drugs and their combination are proarrhythmic, examining arrhythmia susceptibility due to action potential (AP) triangulation and spatial dispersion of action potential duration (APD). Additionally, we aimed to elucidate that Torsades de Pointe (TdP) associated with long-QT are not necessarily caused by early-after-depolarization (EADs) but are related to the presence of AP alternans in both time and space. Isolated Guinea Pig hearts were Langendorff perfused, and optical mapping was done with a voltage dye-sensitive dye. Two commonly used drugs at the beginning of the COVID-19 pandemic, hydroxychloroquine (HCQ) and Azithromycin (AZM), were added to study the effects of QT interval prolongation. Alternans in time and space were characterized by performing restitution pacing protocols. Comparing APs, HCQ prolongs APD during phase-III repolarization, resulting in a higher triangulation ratio than AZM alone or AZM combined with HCQ. Lower triangulation ratios with AZM are associated with phase-II prolongation, lower arrhythmia, and lower incidence of spatially discordant alternans.

Interactive Simulation of the ECG: Effects of Cell Types, Distributions, Shapes and Duration.

The shape of the ECG depends on the lead positions but also on the distribution and dispersion of different cell types and their action potential (AP) durations and shapes. We present an interactive JavaScript program that allows fast simulations of the ECG by solving and displaying the dynamics of cardiac cells in tissue using a web browser. We use physiologically accurate ODE models of cardiac cells of different types including SA node, right and left atria, AV node, Purkinje, and right and left ventricular cells with dispersion that accounts for apex-to-base and epi-to-endo variations. The software allows for real-time variations for each cell type and their spatial range so as to identify how the shape of the ECG varies as a function of cell type, distribution, excitation duration and AP shape. The propagation of the wave is visualized in real time through all the regions as parameters are kept fixed or varied to modify ECG morphology. The code solves thousands of simulated cells in real time and is independent of operating system, so it can run on PCs, laptops, tablets and cellphones. This program can be used to teach students, fellows and the general public how and why lead positions and the different cell physiology in the heart affect the various features of the ECG.

Unimapper: An Online Interactive Analyzer/Visualizer of Optical Mapping Experimental Data.

Time series of spatially-extended two-dimensional recordings are the cornerstone of basic and clinical cardiac electrophysiology. The data source may be either multipolar catheters, multi-electrode arrays, optical mapping with the help of voltage and calcium-sensitive fluorescent dyes, or the output of simulation studies. The resulting data cubes (usually two spatial and one temporal dimension) are shared either as movie files or, after additional processing, various graphs and tables. However, such data products can only convey a limited view of the data. It will be beneficial if the data consumers can interactively process the data, explore different processing options and change its visualization. This paper presents the Unified Electrophysiology Mapping Framework (Unimapper) to facilitate the exchange of electrophysiology data. Its pedigree includes a Java-based optical mapping application. The core of Unimapper is a website and a collection of JavaScript utility functions for data import and visualization (including multi-channel visualization for simultaneous voltage/calcium mapping), basic image processing (e.g., smoothing), basic signal processing (e.g., signal detrending), and advanced processing (e.g., phase calculation using the Hilbert transform). Additionally, Unimapper can optionally use graphics processing units (GPUs) for computationally intensive operations. The Unimapper ecosystem also includes utility libraries for commonly used scientific programming languages (MATLAB, Python, and Julia) that allow the data producers to convert images and recorded signals into a standard format readable by Unimapper. Unimapper can act as a nexus to share electrophysiology data - whether recorded experimentally, clinically or generated by simulation - and enhance communication and collaboration among researchers.

Interactive 3D Human Heart Simulations on Segmented Human MRI Hearts.

Understanding cardiac arrhythmic mechanisms and developing new strategies to control and terminate them using computer simulations requires realistic physiological cell models with anatomically accurate heart structures. Furthermore, numerical simulations must be fast enough to study and validate model and structure parameters. Here, we present an interactive parallel approach for solving detailed cell dynamics in high-resolution human heart structures with a local PC's GPU. In vitro human heart MRI scans were manually segmented to produce 3D structures with anatomically realistic electrophysiology. The Abubu.js library was used to create an interactive code to solve the OVVR human ventricular cell model and the FDA extension of the model in the human MRI heart structures, allowing the simulation of reentrant waves and investigation of their dynamics in real time. Interactive simulations of a physiological cell model in a detailed anatomical human heart reveals propagation of waves through the fine structures of the trabeculae and pectinate muscle that can perpetuate arrhythmias, thereby giving new insights into effects that may need to be considered when planning ablation and other defibrillation methods.

Quantifying arrhythmic long QT effects of hydroxychloroquine and azithromycin with whole-heart optical mapping and simulations.

BACKGROUND: In March 2020, hydroxychloroquine (HCQ) alone or combined with azithromycin (AZM) was authorized as a treatment for COVID-19 in many countries. The therapy proved ineffective with long QT and deadly cardiac arrhythmia risks, illustrating challenges to determine the new safety profile of repurposed drugs. OBJECTIVE: To investigate proarrhythmic effects and mechanism of HCQ and AZM (combined and alone) with high doses of HCQ as in the COVID-19 clinical trials. METHODS: Proarrhythmic effects of HCQ and AZM are quantified using optical mapping with voltage-sensitive dyes in ex vivo Langendorff-perfused guinea pig (GP) hearts and with numerical simulations of a GP Luo-Rudy and a human O'Hara-Virag-Varro-Rudy models, for Epi, Endo, and M cells, in cell and tissue, incorporating the drug's effect on cell membrane ionic currents. RESULTS: Experimentally, HCQ alone and combined with AZM leads to long QT intervals by prolonging the action potential duration and increased spatial dispersion of action potential (AP) repolarization across the heart, leading to proarrhythmic discordant alternans. AZM alone had a lesser arrhythmic effect with less triangulation of the AP shape. Mathematical cardiac models fail to reproduce most of the arrhythmic effects observed experimentally. CONCLUSIONS: During public health crises, the risks and benefits of new and repurposed drugs could be better assessed with alternative experimental and computational approaches to identify proarrhythmic mechanisms. Optical mapping is an effective framework suitable to investigate the drug's adverse effects on cardiac cell membrane ionic channels at the cellular level and arrhythmia mechanisms at the tissue and whole-organ level.