Role of Computed Tomography in Cardiac Electrophysiology.

With the increasing prevalence of arrhythmias, the use of electrophysiology (EP) procedures has increased. Recent advancements in computed tomography (CT) technology have expanded its use in pre-assessments and post-assessments of EP procedures. CT provides high-resolution images, is noninvasive, and is widely available. This article highlights the strengths and weaknesses of cardiac CT in EP.

Optical mapping and optogenetics in cardiac electrophysiology research and therapy: a state-of-the-art review.

State-of-the-art innovations in optical cardiac electrophysiology are significantly enhancing cardiac research. A potential leap into patient care is now on the horizon. Optical mapping, using fluorescent probes and high-speed cameras, offers detailed insights into cardiac activity and arrhythmias by analysing electrical signals, calcium dynamics, and metabolism. Optogenetics utilizes light-sensitive ion channels and pumps to realize contactless, cell-selective cardiac actuation for modelling arrhythmia, restoring sinus rhythm, and probing complex cell-cell interactions. The merging of optogenetics and optical mapping techniques for 'all-optical' electrophysiology marks a significant step forward. This combination allows for the contactless actuation and sensing of cardiac electrophysiology, offering unprecedented spatial-temporal resolution and control. Recent studies have performed all-optical imaging ex vivo and achieved reliable optogenetic pacing in vivo, narrowing the gap for clinical use. Progress in optical electrophysiology continues at pace. Advances in motion tracking methods are removing the necessity of motion uncoupling, a key limitation of optical mapping. Innovations in optoelectronics, including miniaturized, biocompatible illumination and circuitry, are enabling the creation of implantable cardiac pacemakers and defibrillators with optoelectrical closed-loop systems. Computational modelling and machine learning are emerging as pivotal tools in enhancing optical techniques, offering new avenues for analysing complex data and optimizing therapeutic strategies. However, key challenges remain including opsin delivery, real-time data processing, longevity, and chronic effects of optoelectronic devices. This review provides a comprehensive overview of recent advances in optical mapping and optogenetics and outlines the promising future of optics in reshaping cardiac electrophysiology and therapeutic strategies.

Overcoming Uncertainties in Electrogram-Based Atrial Fibrillation Mapping: A Review.

In clinical rhythmology, intracardiac bipolar electrograms (EGMs) play a critical role in investigating the triggers and substrates inducing and perpetuating atrial fibrillation (AF). However, the interpretation of bipolar EGMs is ambiguous due to several aspects of electrodes, mapping algorithms and wave propagation dynamics, so it requires several variables to describe the effects of these uncertainties on EGM analysis. In this narrative review, we critically evaluate the potential impact of such uncertainties on the design of cardiac mapping tools on AF-related substrate characterization. Literature suggest uncertainties are due to several variables, including the wave propagation vector, the wave's incidence angle, inter-electrode spacing, electrode size and shape, and tissue contact. The preprocessing of the EGM signals and mapping density will impact the electro-anatomical representation and the features extracted from the local electrical activities. The superposition of multiple waves further complicates EGM interpretation. The inclusion of these uncertainties is a nontrivial problem but their consideration will yield a better interpretation of the intra-atrial dynamics in local activation patterns. From a translational perspective, this review provides a concise but complete overview of the critical variables for developing more precise cardiac mapping tools.

Assessment of the Interelectrode Distance Effect over the Omnipole with High Multielectrode Arrays.

The development of high-density multielectrode catheters has significantly advanced cardiac electrophysiology mapping. High-density grid catheters have enabled the creation of a novel technique for reconstructing electrogram (EGM) signals known as "omnipole," which is believed to be more reliable than other methods, especially in terms of orientation independence. This study aims to evaluate how distance affects the omnipolar reconstruction of EGMs by comparing different configurations. Using an animal set up of perfused isolated rabbit hearts, recordings were taken using an ad hoc high-density epicardial multielectrode catheter. Inter-electrode distances ranging from 1 to 4 mm were analysed for their effect on the quality of resulting EGMs. Two biomarkers were computed to evaluate the robustness of the reconstructions: the areas contained within the bipolar loops and the amplitudes of the omnipoles. We hypothesised that both bipolar and omnipolar electrograms would be more robust at shorter inter-electrode distances. The results showed that an increase in distance triggers an increase in loop areas and amplitudes, which supports the hypothesis. This finding provides a more reliable estimate of wavefront propagation for the cross-omnipolar reconstruction method. These results emphasise the importance of distance in cardiac electrophysiology mapping and provide valuable insights into the use of high-density multielectrode catheters for EGM reconstruction.Clinical Relevance- The results of this study have direct clinical relevance in the application of the described techniques to recording systems in the cardiac electrophysiology laboratory, enabling clinicians to obtain more precise characterisation of signals in the myocardium.

Chinese expert consensus on the construction of the fluoroless cardiac electrophysiology laboratory and related techniques.

Transcatheter radiofrequency ablation has been widely introduced for the treatment of tachyarrhythmias. The demand for catheter ablation continues to grow rapidly as the level of recommendation for catheter ablation. Traditional catheter ablation is performed under the guidance of X-rays. X-rays can help display the heart contour and catheter position, but the radiobiological effects caused by ionizing radiation and the occupational injuries worn caused by medical staff wearing heavy protective equipment cannot be ignored. Three-dimensional mapping system and intracardiac echocardiography can provide detailed anatomical and electrical information during cardiac electrophysiological study and ablation procedure, and can also greatly reduce or avoid the use of X-rays. In recent years, fluoroless catheter ablation technique has been well demonstrated for most arrhythmic diseases. Several centers have reported performing procedures in a purposefully designed fluoroless electrophysiology catheterization laboratory (EP Lab) without fixed digital subtraction angiography equipment. In view of the lack of relevant standardized configurations and operating procedures, this expert task force has written this consensus statement in combination with relevant research and experience from China and abroad, with the aim of providing guidance for hospitals (institutions) and physicians intending to build a fluoroless cardiac EP Lab, implement relevant technologies, promote the standardized construction of the fluoroless cardiac EP Lab.

Knockdown of the TRPM4 channel alters cardiac electrophysiology and hemodynamics in a sex- and age-dependent manner in mice.

TRPM4 is a calcium-activated, voltage-modulated, nonselective ion channel widely expressed in various cells and tissues. TRPM4 regulates the influx of sodium ions, thus playing a role in regulating the membrane potential. In the heart, TRPM4 is expressed in both cardiomyocytes and cells of the conductive pathways. Clinical studies have linked TRPM4 mutations to several cardiac disorders. While data from experimental studies have demonstrated TRPM4's functional significance in cardiac physiology, its exact roles in the heart have remained unclear. In this study, we investigated the role of TRPM4 in cardiac physiology in a newly generated Trpm4 knockdown mouse model. Male and female Trpm4 knockdown (Trpm4-/- ) and wild-type mice of different ages (5- to 12- week-old (young) and 24-week-old or more (adult)) were characterized using a multimodal approach, encompassing surface electrocardiograms (ECG), echocardiography recordings, ex vivo ECGs in isolated heart, endocardial mappings, Western blots, and mRNA quantifications. The assessment of cardiac electrophysiology by surface ECGs revealed no significant differences between wild-type and Trpm4-/- young (5- to 12-week-old) mice of either sex. Above 24 weeks of age, adult male Trpm4-/- mice showed reduced heart rate and increased heart rate variability. Echocardiography revealed that only adult male Trpm4-/- mice exhibited slight left ventricular hypertrophic alterations compared to controls, illustrated by alterations of the mitral valve pressure halftime, the mitral valve E/A ratio, the isovolumetric relaxation time, and the mitral valve deceleration. In addition, an assessment of the right ventricular systolic function by scanning the pulmonary valve highlighted an alteration in pulmonary valve peak velocity and pressure in adult male Trpm4-/- mice. Endocardial mapping recordings showed that applying 5 µM of the new TRPM4 inhibitor NBA triggered a third-degree atrioventricular block on 40% of wild-type hearts. These results confirm the key role of TRPM4 in the proper structure and electrical function of the heart. It also reveals differences between male and female animals that have never been reported. In addition, the investigation of the effects of NBA on heart function confirms the role of TRPM4 in atrioventricular conduction.

The Role of TRPM4 in Cardiac Electrophysiology and Arrhythmogenesis.

The transient receptor potential melastatin 4 (TRPM4) channel is a non-selective cation channel that activates in response to increased intracellular Ca2+ levels but does not allow Ca2+ to pass through directly. It plays a crucial role in regulating diverse cellular functions associated with intracellular Ca2+ homeostasis/dynamics. TRPM4 is widely expressed in the heart and is involved in various physiological and pathological processes therein. Specifically, it has a significant impact on the electrical activity of cardiomyocytes by depolarizing the membrane, presumably via Na+ loading. The TRPM4 channel likely contributes to the development of cardiac arrhythmias associated with specific genetic backgrounds and cardiac remodeling. This short review aims to overview what is known so far about the TRPM4 channel in cardiac electrophysiology and arrhythmogenesis, highlighting its potential as a novel therapeutic target to effectively prevent and treat cardiac arrhythmias.

Practical guidance to reduce radiation exposure in electrophysiology applying ultra low-dose protocols: a European Heart Rhythm Association review.

Interventional electrophysiology offers a great variety of treatment options to patients suffering from symptomatic cardiac arrhythmia. Catheter ablation of supraventricular and ventricular tachycardia has globally evolved a cornerstone in modern arrhythmia management. Complex interventional electrophysiological procedures engaging multiple ablation tools have been developed over the past decades. Fluoroscopy enabled interventional electrophysiologist throughout the years to gain profound knowledge on intracardiac anatomy and catheter movement inside the cardiac cavities and hence develop specific ablation approaches. However, the application of X-ray technologies imposes serious health risks to patients and operators. To reduce the use of fluoroscopy during interventional electrophysiological procedures to the possibly lowest degree and to establish an optimal protection of patients and operators in cases of fluoroscopy is the main goal of modern radiation management. The present manuscript gives an overview of possible strategies of fluoroscopy reduction and specific radiation protection strategies.

Structural mechanism of human oncochannel TRPV6 inhibition by the natural phytoestrogen genistein.

Calcium-selective oncochannel TRPV6 is the major driver of cell proliferation in human cancers. While significant effort has been invested in the development of synthetic TRPV6 inhibitors, natural channel blockers have been largely neglected. Here we report the structure of human TRPV6 in complex with the plant-derived phytoestrogen genistein, extracted from Styphnolobium japonicum, that was shown to inhibit cell invasion and metastasis in cancer clinical trials. Despite the pharmacological value, the molecular mechanism of TRPV6 inhibition by genistein has remained enigmatic. We use cryo-EM combined with electrophysiology, calcium imaging, mutagenesis, and molecular dynamics simulations to show that genistein binds in the intracellular half of the TRPV6 pore and acts as an ion channel blocker and gating modifier. Genistein binding to the open channel causes pore closure and a two-fold symmetrical conformational rearrangement in the S4-S5 and S6-TRP helix regions. The unprecedented mechanism of TRPV6 inhibition by genistein uncovers new possibilities in structure-based drug design.

A simple and efficient adaptive time stepping technique for low-order operator splitting schemes applied to cardiac electrophysiology.

We present a simple, yet efficient adaptive time stepping scheme for cardiac electrophysiology (EP) simulations based on standard operator splitting techniques. The general idea is to exploit the relation between the splitting error and the reaction's magnitude-found in a previous one-dimensional analytical study by Spiteri and Ziaratgahi-to construct the new time step controller for three-dimensional problems. Accordingly, we propose to control the time step length of the operator splitting scheme as a function of the reaction magnitude, in addition to the common approach of adapting the reaction time step. This conforms with observations in numerical experiments supporting the need for a significantly smaller time step length during depolarization than during repolarization. The proposed scheme is compared with classical proportional-integral-differential controllers using state-of-the-art error estimators, which are also presented in details as they have not been previously applied in the context of cardiac EP with operator splitting techniques. Benchmarks show that choosing the time step as a sigmoidal function of the reaction magnitude is highly efficient and full cardiac cycles can be computed with precision even in a realistic biventricular setup. The proposed scheme outperforms common adaptive time stepping techniques, while depending on fewer tuning parameters.

An inner-outer subcycling algorithm for parallel cardiac electrophysiology simulations.

This paper explores cardiac electrophysiological simulations of the monodomain equations and introduces a novel subcycling time integration algorithm to exploit the structure of the ionic model. The aim of this work is to improve upon the efficiency of parallel cardiac monodomain simulations by using our subcycling algorithm in the computation of the ionic model to handle the local sharp changes of the solution. This will reduce the turnaround time for the simulation of basic cardiac electrical function on both idealized and patient-specific geometry. Numerical experiments show that the proposed approach is accurate and also has close to linear parallel scalability on a computer with more than 1000 processor cores. Ultimately, the reduction in simulation time can be beneficial in clinical applications, where multiple simulations are often required to tune a model to match clinical measurements.

Efficient time splitting schemes for the monodomain equation in cardiac electrophysiology.

Approximating the fast dynamics of depolarization waves in the human heart described by the monodomain model is numerically challenging. Splitting methods for the PDE-ODE coupling enable the computation with very fine space and time discretizations. Here, we compare different splitting approaches regarding convergence, accuracy, and efficiency. Simulations were performed for a benchmark problem with the Beeler-Reuter cell model on a truncated ellipsoid approximating the left ventricle including a localized stimulation. For this configuration, we provide a reference solution for the transmembrane potential. We found a semi-implicit approach with state variable interpolation to be the most efficient scheme. The results are transferred to a more physiological setup using a bi-ventricular domain with a complex external stimulation pattern to evaluate the accuracy of the activation time for different resolutions in space and time.

Calibrating cardiac electrophysiology models using latent Gaussian processes on atrial manifolds.

Models of electrical excitation and recovery in the heart have become increasingly detailed, but have yet to be used routinely in the clinical setting to guide personalized intervention in patients. One of the main challenges is calibrating models from the limited measurements that can be made in a patient during a standard clinical procedure. In this work, we propose a novel framework for the probabilistic calibration of electrophysiology parameters on the left atrium of the heart using local measurements of cardiac excitability. Parameter fields are represented as Gaussian processes on manifolds and are linked to measurements via surrogate functions that map from local parameter values to measurements. The posterior distribution of parameter fields is then obtained. We show that our method can recover parameter fields used to generate localised synthetic measurements of effective refractory period. Our methodology is applicable to other measurement types collected with clinical protocols, and more generally for calibration where model parameters vary over a manifold.

Neural Correlates of Motor Imagery during Action Observation in Affordance-based Actions: Preliminary Results.

Object affordance, a characterization of the different functionalities of an object, refers to an object's numerous possibilities of interaction. It has a significant part to play in priming motoric actions which depends on the actor's spontaneous neurological behaviour. Action Observation (AO) and Motor Imagery (MI) also lead to the stimulation of motor system. In fact, AO and MI result in activation of overlapping brain areas as the actual motor task. AO combined with MI (referred to as AO+MI) initiates higher cortical activity in comparison with either MI or AO alone. In this paper, we investigate the influence of affordance driven motor priming during AO, MI and AO + MI. Source current density as an EEG parameter is estimated by Low Resolution Electromagnetic Tomography (LORETA). Our results demonstrate that affordance driven motor priming during AO+MI indicates stronger electrophysiological and behavioural changes. This is evident from the N2 ERP component. Further, the current source density (in brain regions associated with motor planning) during affordance driven AO+MI is found to be maximum.