Functional substrate mapping of atrium in patients with atrial scar: A novel method to predict critical isthmus of atrial tachycardia.

Atrial tachycardia (AT) is a common rhythm disorder, especially in patients with atrial structural abnormalities. Although voltage mapping can provide a general picture of structural alterations which are mainly secondary to prior ablations, surgery or pressure/volume overload, data is scarce regarding the functional characteristics of low voltage regions in the atrium to predict critical isthmus of ATs. Recently, functional substrate mapping (FSM) emerged as a potential tool to evaluate the functionality of structurally altered regions in the atrium to predict critical sites of reentry. Current evidence suggested a clear association between deceleration zones of isochronal late activation mapping (ILAM) during sinus/paced rhythm and critical isthmus of reentry in patients with left AT. Therefore, these areas seem to be potential ablation targets even not detected during AT. Furthermore, abnormal conduction detected by ILAM may also have a role to identify the potential substrate and predict atrial fibrillation outcome after pulmonary vein isolation. Despite these promising findings, the utility of such an approach needs to be evaluated in large-scale comparative studies. In this review, we aimed to share our experience and review the current literature regarding the use of FSM during sinus/paced rhythm in the prediction of re-entrant ATs and discuss future implications and potential use in patients with atrial low-voltage areas.

POPDC1 Variants Cause Atrioventricular Node Dysfunction and Arrhythmogenic Changes in Cardiac Electrophysiology and Intracellular Calcium Handling in Zebrafish.

Popeye domain-containing (POPDC) proteins selectively bind cAMP and mediate cellular responses to sympathetic nervous system (SNS) stimulation. The first discovered human genetic variant (POPDC1S201F) is associated with atrioventricular (AV) block, which is exacerbated by increased SNS activity. Zebrafish carrying the homologous mutation (popdc1S191F) display a similar phenotype to humans. To investigate the impact of POPDC1 dysfunction on cardiac electrophysiology and intracellular calcium handling, homozygous popdc1S191F and popdc1 knock-out (popdc1KO) zebrafish larvae and adult isolated popdc1S191F hearts were studied by functional fluorescent analysis. It was found that in popdc1S191F and popdc1KO larvae, heart rate (HR), AV delay, action potential (AP) and calcium transient (CaT) upstroke speed, and AP duration were less than in wild-type larvae, whereas CaT duration was greater. SNS stress by ß-adrenergic receptor stimulation with isoproterenol increased HR, lengthened AV delay, slowed AP and CaT upstroke speed, and shortened AP and CaT duration, yet did not result in arrhythmias. In adult popdc1S191F zebrafish hearts, there was a higher incidence of AV block, slower AP upstroke speed, and longer AP duration compared to wild-type hearts, with no differences in CaT. SNS stress increased AV delay and led to further AV block in popdc1S191F hearts while decreasing AP and CaT duration. Overall, we have revealed that arrhythmogenic effects of POPDC1 dysfunction on cardiac electrophysiology and intracellular calcium handling in zebrafish are varied, but already present in early development, and that AV node dysfunction may underlie SNS-induced arrhythmogenesis associated with popdc1 mutation in adults.

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.

Impact of artificial intelligence arrhythmia mapping on time to first ablation, procedure duration, and fluoroscopy use.

INTRODUCTION: Artificial intelligence (AI) ECG arrhythmia mapping provides arrhythmia source localization using 12-lead ECG data; whether this information impacts procedural efficiency is unknown. We performed a retrospective, case-control study to evaluate the hypothesis that AI ECG mapping may reduce time to ablation, procedural duration, and fluoroscopy. MATERIALS AND METHODS: Cases in which system output was used were retrospectively enrolled according to IRB-approved protocols at each site. Matched control cases were enrolled in reverse chronological order beginning on the last day for which the technology was unavailable. Controls were matched based upon physician, institution, arrhythmia, and a predetermined complexity rating. Procedural metrics, fluoroscopy data, and clinical outcomes were assessed from time-stamped medical records. RESULTS: The study group consisted of 28 patients (age 65 ± 11 years, 46% female, left atrial dimension 4.1 ± 0.9 cm, LVEF 50 ± 18%) and was similar to 28 controls. The most common arrhythmia types were atrial fibrillation (n = 10), premature ventricular complexes (n = 8), and ventricular tachycardia (n = 6). Use of the system was associated with a 19.0% reduction in time to ablation (133 ± 48 vs. 165 ± 49 min, p = 0.02), a 22.6% reduction in procedure duration (233 ± 51 vs. 301 ± 83 min, p < 0.001), and a 43.7% reduction in fluoroscopy (18.7 ± 13.3 vs. 33.2 ± 18.0 min, p < 0.001) versus controls. At 6 months follow-up, arrhythmia-free survival was 73.5% in the study group and 63.3% in the control group (p = 0.56). CONCLUSION: Use of forward-solution AI ECG mapping is associated with reductions in time to first ablation, procedure duration, and fluoroscopy without an adverse impact on procedure outcomes or complications.

Voltage and propagation mapping: New tools to improve successful ablation of atrioventricular nodal reentry tachycardia.

INTRODUCTION: Mapping system is useful in ablation of atrioventricular nodal reentry tachycardia (AVNRT) and localization of anatomic variances. Voltage mapping identifies a low voltage area in the Koch triangle called low-voltage-bridge (LVB); propagation mapping identifies the collision point (CP) of atrial wavefront convergence. We conducted a prospective study to evaluate the relationship between LVB and CP with successful site of ablation and identify standard value for LVB. MATERIALS AND METHODS: Three-dimensional (3D) maps of the right atria were constructed from intracardiac recordings using the ablation catheter. Cut-off values on voltage map were adjusted until LVB was observed. On propagation map, atrial wavefronts during sinus rhythm collide in the site representing CP, indicating the area of slow pathway conduction. Ablation site was selected targeting LVB and CP site, confirmed by anatomic position on fluoroscopy and atrioventricular ratio. RESULTS: Twenty-seven consecutive patients were included. LVB and CP were present in all patients. Postprocedural evaluation identified standard cut-off of 0.3-1 mV useful for LVB identification. An overlap between LVB and CP was observed in 23 (85%) patients. Procedure success was achieved in all patient with effective site at first application in 22 (81%) patients. There was a significant correlation between LVB, CP, and the site of effective ablation (p = .001). CONCLUSION: We found correlation between LVB and CP with the site of effective ablation, identifying a voltage range useful for standardized LVB identification. These techniques could be useful to identify ablation site and minimize radiation exposure.

Peak frequency mapping of atypical atrial flutter.

INTRODUCTION: Peak frequency (PF) mapping is a novel method that may identify critical portions of myocardial substrate supporting reentry. The aim of this study was to describe and evaluate PF mapping combined with omnipolar voltage mapping in the identification of critical isthmuses of left atrial (LA) atypical flutters. METHODS AND RESULTS: LA omnipolar voltage and PF maps were generated in flutter using the Advisor HD-Grid catheter (Abbott) and EnSite Precision Mapping System (Abbott) in 12 patients. Normal voltage was defined as ≥0.5 mV, low-voltage as 0.1-0.5 mV, and scar as <0.1 mV. PF distributions were compared with ANOVA and post hoc Tukey analyses. The 1 cm radius from arrhythmia termination was compared to global myocardium with unpaired t-testing. The mean age was 65.8 ± 9.7 years and 50% of patients were female. Overall, 34 312 points were analyzed. Atypical flutters most frequently involved the mitral isthmus (58%) or anterior wall (25%). Mean PF varied significantly by myocardial voltage: normal (335.5 ± 115.0 Hz), low (274.6 ± 144.0 Hz), and scar (71.6 ± 140.5 Hz) (p < .0001 for all pairwise comparisons). All termination sites resided in low-voltage regions containing intermediate or high PF. Overall, mean voltage in the 1 cm radius from termination was significantly lower than the remaining myocardium (0.58 vs. 0.95 mV, p < .0001) and PF was significantly higher (326.4 vs. 245.1 Hz, p < .0001). CONCLUSION: Low-voltage, high-PF areas may be critical targets during catheter ablation of atypical atrial flutter.

Endocardial repolarization dispersion in BrS: A novel automatic algorithm for mapping activation recovery interval.

INTRODUCTION: Repolarization dispersion in the right ventricular outflow tract (RVOT) contributes to the type-1 electrocardiographic (ECG) phenotype of Brugada syndrome (BrS), while data on the significance and feasibility of mapping repolarization dispersion in BrS patients are scarce. Moreover, the role of endocardial repolarization dispersion in BrS is poorly investigated. We aimed to assess endocardial repolarization patterns through an automated calculation of activation recovery interval (ARI) estimated on unipolar electrograms (UEGs) in spontaneous type-1 BrS patients and controls; we also investigated the relation between ARI and right ventricle activation time (RVAT), and T-wave peak-to-end interval (Tpe) in BrS patients. METHODS: Patients underwent endocardial high-density electroanatomical mapping (HDEAM); BrS showing an overt type-1 ECG were defined as OType1, while those without (latent type-1 ECG and LType1) received ajmaline infusion. BrS patients only underwent programmed ventricular stimulation (PVS). Data were elaborated to obtain ARI corrected with the Bazett formula (ARIc), while RVAT was derived from activation maps. RESULTS: 39 BrS subjects (24 OType1 and 15 LTtype1) and 4 controls were enrolled. OType1 and post-ajmaline LType1 showed longer mean ARIc than controls (306 ± 27.3 ms and 333.3 ± 16.3 ms vs. 281.7 ± 10.3 ms, p = .05 and p < .001, respectively). Ajmaline induced a significant prolongation of ARIc compared to pre-ajmaline LTtype1 (333.3 ± 16.3 vs. 303.4 ± 20.7 ms, p < .001) and OType1 (306 ± 27.3 ms, p < .001). In patients with type-1 ECG (OTtype1 and post-ajmaline LType1) ARIc correlated with RVAT (r = .34, p = .04) and Tpec (r = .60, p < .001), especially in OType1 subjects (r = .55, p = .008 and r = .65 p < .001, respectively). CONCLUSION: ARIc mapping demonstrates increased endocardial repolarization dispersion in RVOT in BrS. Endocardial ARIc positively correlates with RVAT and Tpec, especially in OType1.

In Vivo Cardiac Electrophysiology in Mice: Determination of Atrial and Ventricular Arrhythmic Substrates.

Cardiac arrhythmias are a common cardiac condition that might lead to fatal outcomes. A better understanding of the molecular and cellular basis of arrhythmia mechanisms is necessary for the development of better treatment modalities. To aid these efforts, various mouse models have been developed for studying cardiac arrhythmias. Both genetic and surgical mouse models are commonly used to assess the incidence and mechanisms of arrhythmias. Since spontaneous arrhythmias are uncommon in healthy young mice, intracardiac programmed electrical stimulation (PES) can be performed to assess the susceptibility to pacing-induced arrhythmias and uncover the possible presence of a proarrhythmogenic substrate. This procedure is performed by positioning an octopolar catheter inside the right atrium and ventricle of the heart through the right jugular vein. PES can provide insights into atrial and ventricular electrical activity and reveal whether atrial and/or ventricular arrhythmias are present or can be induced. Here, we explain detailed procedures used to perform this technique, possible troubleshooting scenarios, and methods to interpret the results obtained. © 2024 Wiley Periodicals LLC. Basic Protocol: Programmed electrical stimulation in mice.

Economic analyses in cardiac electrophysiology: from clinical efficacy to cost utility.

Cardiac electrophysiology is an evolving field that relies heavily on costly device- and catheter-based technologies. An increasing number of patients with heart rhythm disorders are becoming eligible for cardiac interventions, not least due to the rising prevalence of atrial fibrillation and increased longevity in the population. Meanwhile, the expansive costs of healthcare face finite societal resources, and a cost-conscious approach to new technologies is critical. Cost-effectiveness analyses support rational decision-making in healthcare by evaluating the ratio of healthcare costs to health benefits for competing therapies. They may, however, be subject to significant uncertainty and bias. This paper aims to introduce the basic concepts, framework, and limitations of cost-effectiveness analyses to clinicians including recent examples from clinical electrophysiology and device therapy.

Multisize Electrode Field-of-View: Validation by High Resolution Gadolinium-Enhanced Cardiac Magnetic Resonance.

BACKGROUND: Voltage mapping to detect ventricular scar is important for guiding catheter ablation, but the field-of-view of unipolar, bipolar, conventional, and microelectrodes as it relates to the extent of viable myocardium (VM) is not well defined. OBJECTIVES: The purpose of this study was to evaluate electroanatomic voltage-mapping (EAVM) with different-size electrodes for identifying VM, validated against high-resolution ex-vivo cardiac magnetic resonance (HR-LGE-CMR). METHODS: A total of 9 swine with early-reperfusion myocardial infarction were mapped with the QDOT microcatheter. HR-LGE-CMR (0.3-mm slices) were merged with EAVM. At each EAVM point, the underlying VM in multisize transmural cylinders and spheres was quantified from ex vivo CMR and related to unipolar and bipolar voltages recorded from conventional and microelectrodes. RESULTS: In each swine, 220 mapping points (Q1, Q3: 216, 260 mapping points) were collected. Infarcts were heterogeneous and nontransmural. Unipolar and bipolar voltage increased with VM volumes from >175 mm3 up to >525 mm3 (equivalent to a 5-mm radius cylinder with height >6.69 mm). VM volumes in subendocardial cylinders with 1- or 3-mm depth correlated poorly with all voltages. Unipolar voltages recorded with conventional and microelectrodes were similar (difference 0.17 ± 2.66 mV) and correlated best to VM within a sphere of radius 10 and 8 mm, respectively. Distance-weighting did not improve the correlation. CONCLUSIONS: Voltage increases with transmural volume of VM but correlates poorly with small amounts of VM, which limits EAVM in defining heterogeneous scar. Microelectrodes cannot distinguish thin from thick areas of subendocardial VM. The field-of-view for unipolar recordings for microelectrodes and conventional electrodes appears to be 8 to 10 mm, respectively, and unexpectedly similar.

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.

Robust Artificial Intelligence Tool for Atrial Fibrillation Diagnosis: Novel Development Approach Incorporating Both Atrial Electrograms and Surface ECG and Evaluation by Head-to-Head Comparison With Hospital-Based Physician ECG Readers.

BACKGROUND: Atrial fibrillation (AF) increases risk of embolic stroke, and in postoperative patients, increases cost of care. Consequently, ECG screening for AF in high-risk patients is important but labor-intensive. Artificial intelligence (AI) may reduce AF detection workload, but AI development presents challenges. METHODS AND RESULTS: We used a novel approach to AI development for AF detection using both surface ECG recordings and atrial epicardial electrograms obtained in postoperative cardiac patients. Atrial electrograms were used only to facilitate establishing true AF for AI development; this permitted the establishment of an AI-based tool for subsequent AF detection using ECG records alone. A total of 5 million 30-second epochs from 329 patients were annotated as AF or non-AF by expert ECG readers for AI training and validation, while 5 million 30-second epochs from 330 different patients were used for AI testing. AI performance was assessed at the epoch level as well as AF burden at the patient level. AI achieved an area under the receiver operating characteristic curve of 0.932 on validation and 0.953 on testing. At the epoch level, testing results showed means of AF detection sensitivity, specificity, negative predictive value, positive predictive value, and F1 (harmonic mean of positive predictive value and sensitivity) as 0.970, 0.814, 0.976, 0.776, and 0.862, respectively, while the intraclass correlation coefficient for AF burden detection was 0.952. At the patient level, AF burden sensitivity and positive predictivity were 96.2% and 94.5%, respectively. CONCLUSIONS: Use of both atrial electrograms and surface ECG permitted development of a robust AI-based approach to postoperative AF recognition and AF burden assessment. This novel tool may enhance detection and management of AF, particularly in patients following operative cardiac surgery.

Catheter ablation for non-paroxysmal atrial fibrillation. A review.

Atrial fibrillation (AF), the most common cardiac arrhythmia is associated with increased morbidity and mortality. The higher mortality is due to the risk of heart failure and cardioembolic events. This in-depth review focuses on the strategies and efficacy of catheter ablation for non-paroxysmal atrial fibrillation. The main medical databases were searched for contemporary studies on catheter ablation for non-paroxysmal AF. Catheter ablation is currently proven to be the most effective treatment for AF and consists of pulmonary vein isolation as the cornerstone plus additional ablations. In terms of SR maintenance, it is less effective in non-paroxysmal AF than in paroxysmal patients. but the clinical benefit in non-paroxysmal patients is substantially higher. Since pulmonary vein isolation is ineffective, a variety of techniques have been developed, e.g. linear ablations, ablation of complex atrial fractionated electrograms, etc. Another paradox consists in the technique of catheter ablation. Despite promising results in early observation studies, further randomized studies have not confirmed the initial enthusiasm. Recently, a new approach, pulsed-field ablation, appears promising. This is an in-depth summary of current technologies and techniques for the ablation of non-paroxysmal AF. We discuss the benefits, risks and implications in the treatment of patients with non-paroxysmal AF.