Electrophysiological Characteristics Research Articles

Spatiomolecular Characterization of Dopamine D2 Receptors Cells in the Mouse External Globus Pallidus.

The external globus pallidus (GPe) is part of the basal ganglia circuit and plays a key role in controlling the actions. Although, many evidence indicate that dopamine through its activation of D2 receptors (D2Rs) modulates the GPe neuronal activity, the precise spatiomolecular characterization of cell populations expressing D2Rs in the mouse GPe is still lacking. By combining single molecule in situ hybridization, cell type-specific imaging analyses, and electrophysiology slice recordings, we found that GPe D2R cells are neurons preferentially localized in the caudal portion of GPe. These neu- rons comprising pallido-striatal, pallido-nigral, and pallido-cortical neurons segregate into two distinct populations displaying molecular and electrophysiological features of GPe GABAergic PV/NKX2.1 and cholinergic neurons respectively. By clarifying the spatial molecular identity of GPe D2R neurons in the mouse, this work provides the basis for future studies aiming at disentangling the action of do- pamine within the GPe.

GLP-1 increases heart rate by a direct action on the sinus node.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used to treat type 2 diabetes and obesity. Albeit cardiovascular outcomes generally improve, treatment with GLP-1 RAs is associated with increased heart rate, the mechanism of which is unclear. We employed a large animal model, the female landrace pig, and used multiple in-vivo and ex-vivo approaches including pharmacological challenges, electrophysiology and high-resolution mass spectrometry to explore how GLP-1 elicits an increase in heart rate. In anaesthetized pigs, neither cervical vagotomy, adrenergic blockers (alpha, beta or combined alpha-beta blockade), ganglionic blockade (hexamethonium) nor inhibition of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels (ivabradine) abolished the marked chronotropic effect of GLP-1. GLP-1 administration to isolated perfused pig hearts also increased heart rate, which was abolished by GLP-1 receptor blockade. Electrophysiological characterization of GLP-1 effects in vivo and in isolated perfused hearts localized electrical modulation to the atria and conduction system. In isolated sinus nodes, GLP-1 administration shortened action potential cycle length of pacemaker cells and shifted the site of earliest activation. The effect was independent of HCN blockade. Collectively, these data support a direct effect of GLP-1 on GLP-1 receptors within the heart. Consistently, single nucleus RNA sequencing (snRNAseq) showed GLP-1 receptor expression in porcine pacemaker cells. Quantitative phosphoproteomics analyses of sinus node samples revealed that GLP-1 administration leads to phosphorylation changes of calcium cycling proteins of the sarcoplasmic reticulum, known to regulate heart rate. GLP-1 has direct chronotropic effects on the heart mediated by GLP-1 receptors in pacemaker cells of the sinus node, inducing changes in action potential morphology and the leading pacemaker site through a calcium signaling response characterized by PKA-dependent phosphorylation of Ca2+ cycling proteins involved in pace making. Targeting the pacemaker calcium clock may be a strategy to lower heart rate in GLP-1 RA recipients.

Microfluidic Biosensor for the In Vitro Electrophysiological Characterization of Actin Bundles

Microfluidic Biosensor for the In Vitro Electrophysiological Characterization of Actin Bundles

Cannabidiol-enriched oil for adult patients with drug-resistant epilepsy: Prospective clinical and electrophysiological study.

Cannabidiol-enriched oil (CBDO) is being used increasingly to improve seizure control in adult patients with drug-resistant epilepsy (DRE), despite the lack of large-scale studies supporting its efficacy in this patient population. We aimed to assess the effects of add-on CBDO on seizure frequency as well as on gait, cognitive, affective, and sleep-quality metrics, and to explore the electrophysiological changes in responder and non-responder DRE patients treated with add-on CBDO. We prospectively recruited adult DRE patients who were treated with add-on CBDO. Patients were evaluated prior to treatment and following 4 weeks of a maintenance daily dose of ≈260 mg CBD and ≈12 mg Δ9-tetrahydrocannabinol (THC). The outcome measures included seizure response to CBDO (defined as ≥50% decrease in seizures compared to pre-CBDO baseline), gait testing, Montreal Cognitive Assessment (MoCA), Hospital Anxiety and Depression Scale (HADS), and sleep-quality questionnaire assessments. Patients underwent electroencephalography (EEG) recording during rest as well as event-related potentials (ERPs) during visual Go/NoGo task while sitting and while walking. Nineteen patients were recruited, of which 16 finished pre- and post-CBDO assessments. Seven patients (43.75%) were responders demonstrating an average reduction of 82.4% in seizures, and nine patients (56.25%) were non-responders with an average seizure increase of 30.1%. No differences in demographics and clinical parameters were found between responders and non-responders at baseline. However, responders demonstrated better performance in the dual-task walking post-treatment (p = .015), and correlation between increase in MoCA and seizure reduction (r = .810, p = .027). Post-CBDO P300 amplitude was lower during No/Go-sitting in non-responders (p = .028) and during No/Go-walking in responders (p = .068). CBDO treatment can reduce seizures in a subset of patients with DRE, but could aggravate seizure control in a minority of patients; yet we found no specific baseline clinical or electrophysiological characteristics that are associated with response to CBDO. However, changes in ERPs in response to treatment could be a promising direction to better identify patients who could benefit from CBDO treatment.

Maturation of Human iPSC-Derived Cardiac Microfiber with Electrical Stimulation Device.

Here an electrical stimulation system is described for maturing microfiber-shaped cardiac tissue (cardiac microfibers, CMFs). The system enables stable culturing of CMFs with electrical stimulation by placing the tissue between electrodes. The electrical stimulation device provides an electric field covering whole CMFs within the stimulation area and can control the beating of the cardiac microfibers. In addition, CMFs under electrical stimulation with different frequencies are examined to evaluate the maturation levels by their sarcomere lengths, electrophysiological characteristics, and gene expression. Sarcomere elongation (14% increase compared to control) is observed at day 10, and a significant upregulation of electrodynamic properties such as gap junction protein alpha 1 (GJA1) and potassium inwardly rectifying channel subfamily J member 2 (KCNJ2) (maximum fourfold increase compared to control) is observed at day 30. These results suggest that electrically stimulated cultures can accelerate the maturation of microfiber-shaped cardiac tissues compared to those without electrical stimulation. This model will contribute to the pathological research of unexplained cardiac diseases and pharmacologic testing by stably constructing matured CMFs.

In vivo calcium and voltage mapping of the zebrafish heart

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Research Foundation Flanders (FWO) Purpose Inherited cardiac arrhythmias are characterized by a disturbance in the normal electrical functioning of the heart due to a dysfunction of cardiac ion channels, accessory proteins and/or structural components. This complex process is difficult to model in vitro, while in vivo mouse models differ substantially from humans with regards to cardiac electrophysiology. Thus, there is a need for alternative disease models in cardiac arrhythmia research. The zebrafish heart shows remarkable similarity to humans in its electrocardiogram and action potential (AP) morphology. Due to the optical translucency of zebrafish larvae, it is possible visualize the cardiac calcium and voltage dynamics across their entire hearts in vivo by use of genetically encoded calcium and voltage indicators (GECI and GEVI). We combined the fast kinetics of a next generation voltage reporter (Ace2N-mNeon) with a spectrally compatible calcium sensor (R-GECO) to create a sensitive high throughput method for in vivo characterization of the cardiac AP. Methods Ace2N-mNeon and R-GECO were expressed under control of a myocardial specific promoter via the Tol2kit system. The effect of sensor expression on normal physiology was assessed by patch clamp experiments. Fluorescence recordings were obtained with a Leica SP8 DLS microscope and a custom-built light sheet microscope. Our zebrafish sensor line was validated by experiments with quinidine drug exposure, as well as a novel model for long QT syndrome (LQTS) with a knock-in (KI) mutation in the cacna1c gene. Results Sensor expression did not significantly alter cardiac electrophysiology. The tg(myl7:Ace2N-mNeon/R-GECO) line demonstrated alterations in the heart rate, depolarization and repolarization induced by quinidine exposure. We observed a significantly prolonged ventricular repolarization in the LQTS KI line. Three-dimensional optical maps of AP characteristics across the entire zebrafish heart exhibited the physiological characteristics of the zebrafish cardiac electrophysiology, with activation initiated at the atrial venous pole and propagated towards the ventricular outflow tract, prolonged repolarization in the ventricles compared to the atria and slowed depolarization in the atrio-ventricular canal. Conclusion By expressing Ace2N-mNeon and R-GECO in the zebrafish heart, we were able to accurately detect drug- and mutation induced alterations in the cardiac AP, as well as AP characteristics across the entire heart, without compromising normal cardiac electrophysiology. Our transgenic line will provide a promising assay for future studies of cardiac arrhythmia.

AAV-mediated Gene Cocktails Enhance Supporting Cell Reprogramming and Hair Cell Regeneration.

Mammalian cochlear hair cells (HCs) are essential for hearing, and damage to HCs results in severe hearing impairment. Damaged HCs can be regenerated by neighboring supporting cells (SCs), thus the functional regeneration of HCs is the main goal for the restoration of auditory function in vivo. Here, cochlear SC trans-differentiation into outer and inner HC by the induced expression of the key transcription factors Atoh1 and its co-regulators Gfi1, Pou4f3, and Six1 (GPAS), which are necessary for SCs that are destined for HC development and maturation via the AAV-ie targeting the inner ear stem cells are successfully achieved. Single-cell nuclear sequencing and lineaging tracing results showed that the majority of new Atoh1-derived HCs are in a state of initiating differentiation, while GP (Gfi1, Pou4f3) and GPS (Gfi1, Pou4f3, and Six1) enhanced the Atoh1-induced new HCs into inner and outer HCs. Moreover, the patch-clamp analysis indicated that newborn inner HCs induced by GPAS forced expression have similar electrophysiological characteristics to those of native inner HCs. Also, GPAS can induce HC regeneration in the HC-damaged mice model. In summary, the study demonstrates that AAV-mediated co-regulation of multiple genes, such as GPAS, is an effective means to achieve functional HC regeneration in the mouse cochlea.

The interpretation of field and LEAP potentials recorded from cardiomyocyte monolayers

Abstract Funding Acknowledgements None. Multi-electrode arrays (MEA) are the method of choice for electrophysiological characterization of cardiomyocyte monolayers. The field potentials recorded using a MEA are like extracellular electrograms recorded from ventricular myocardium using conventional electrodes. Nevertheless, different criteria are often used to interpret field potential and extracellular electrogram, which hampers correct interpretation and translation to the patient. To validate criteria for extracellular electrograms analysis applicable to field potentials, we used neonatal rat cardiomyocytes to generate monolayers. We recorded field potentials using a MEA and simultaneously recorded action potentials using sharp micro-electrodes. In parallel we recreated our experimental setting in silico and performed simulations. We demonstrate that the amplitude of the local RS-complex of a field potential correlated with conduction velocity, but only in the lower ranges of conduction velocities. The time of the peak of the T-wave of the field potentials correlated well with APD90 and the time of the steepest upslope with APD50. By injecting current into the monolayer, we could record a local extracellular action potential (LEAP). The LEAP was of low amplitude and highly depolarized, and the shape differed markedly from the shape of the local action potential. Criteria for interpreting extra cellular electrograms should also be applied to field potentials. This will provide a strong basis for analysis of heterogeneity in conduction velocity and repolarization in cultured monolayers of cardiomyocytes especially at low conduction velocities. A LEAP is not a recording of the local action potential but is generated by intracellular current provided by neighboring cardiomyocytes.

Impacts of DCM-linked gating pore currents on the electrophysiological characteristics of hiPSC-CM monolayers

BackgroundVariants of the SCN5A gene, which encodes the NaV1.5 cardiac sodium channel, have been linked to arrhythmic disorders associated with dilated cardiomyopathy (DCM). However, the precise pathological mechanisms remain elusive. The present study aimed to elucidate the pathophysiological consequences of the DCM-linked Nav1.5/R219H variant, which is known to generate a gating pore current, using patient-specific human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) cultured in monolayers. MethodsVentricular- and atrial-like hiPSC-CM monolayers were generated from DCM patients carrying the R219H SCN5A variant as well as from healthy control individuals. CRISPR-corrected hiPSC-CMs served as isogenic controls. Simultaneous optical mapping of action potentials (APs) and calcium transients (CaTs) was employed to measure conduction velocities (CVs) and AP durations (APDs) and served as markers of electrical excitability. Calcium handling was evaluated by assessing CaT uptake (half-time to peak), recapture (tau of decay), and durations (TD50 and TD80). A multi-electrode array (MEA) analysis was conducted on hiPSC-CM monolayers to measure field potential (FP) parameters, including corrected Fridericia FP durations (FPDc). ResultsOur results revealed that CVs were significantly reduced by more than 50 % in both ventricular- and atrial-like hiPSC-CM monolayers carrying the R219H variant compared to the control group. APDs were also prolonged in the R219H group compared to the control and CRISPR-corrected groups. CaT uptake, reuptake, and duration were also markedly delayed in the R219H group compared to the control and CRISPR-corrected groups in both the ventricular- and the atrial-like hiPSC-CM monolayers. Lastly, the MEA data revealed a notably prolonged FPDc in the ventricular- and atrial-like hiPSC-CMs carrying the R219H variant compared to the control and isogenic control groups. ConclusionsThese findings highlight the impact of the gating pore current on AP propagation and calcium homeostasis within a functional syncytium environment and offer valuable insights into the potential mechanisms underlying DCM pathophysiology.

Electrophysiological characteristics and durability of index pulsed field ablation lesions from redo procedures for atrial arrhythmia recurrences

Abstract Background Catheter ablation for atrial fibrillation (AF) has been performed using mainly thermal energy sources (radiofrequency, cryo, or laser). Pulsed field ablation (PFA) is a novel energy with interesting safety and effectiveness demonstrated in previous preclinical and clinical trials. Purpose We sought to assess the electrophysiological characteristics and durability of PFA index procedure procedures using a pentaspline PFA catheter as assessed based on redo procedures in patients with AT/AF recurrences. Methods A total of 169 patients (paroxysmal AF (PAF), 120; persistent AF (PsAF), 49) who underwent PFA using a pentaspline PFA catheter in the index procedure from November 2021 to July 2023 were studied. Pulmonary vein isolation (PVI) was performed with PFA in all patients with additional PFA lines: i)posterolateral mitral isthmus (MI) ablation in 25, ii) posterior line in 40 patients. Twenty-seven patients (PAF, 11; PsAF, 16) had atrial arrhythmia (atrial tachycardia (AT) or AF) recurrence after a 3-month blanking period (16%). We analyzed the electrophysiological characteristics of previous PFA lesions in 18 (PAF, 8; PsAF, 10) out of 27 patients in whom an activation and voltage mapping using 3-D electroanatomical mapping system was available. Results PV reconnections were identified in 7 of 18 patients (13PVs/69PVs ,18.8%) at the PV-LA junctions and carina regions of both left PVs and right PVs, mainly at the anterior aspect of right PV carina (n=6). In 6 out of 10 redo cases, posterolateral MI line using PFA was performed in the index procedure based on our strategy for PsAF ablation. In these 6 cases with previous MI line using PFA for PsAF ablation endocardial PFA was combined with marshall vein ethanolization(Et-VOM). Additional RF endocardial ablation and in the CS was needed to achieve MI block in 2 (33%) in the index procedure. 3D mapping of redo cases showed MI line gaps in 6/6 (100%). In 3 of those patients, the clinical arrhythmia recurrence was a perimitral AT (50%). Nine of the 10 PsAF patients who underwent a redo procedure had an index procedure complete posterior line. Remapping demonstrated durable block in 7/9 (78%). One of these patients presented with a roof dependent AT diagnosed in the redo procedure. Durable posterior lines received a significantly larger number of PFA deliveries during the index procedure: 16.4±3.3 vs 10.0±2.8 respectively, p=0.041). Conclusion This study based on redo cases after PFA using a pentaspline PFA catheter shows that PFA is associated with high durability for PVI and posterior line ablation. However the durability of MI line are poor, even when combined with VOM ethanolization. Further research is needed to define the optimal number of deliveries required to achieve durable posterior line block.

Electrophysiologic characteristics and outcomes of atrial tachycardia ablation after mitral valve surgery

Abstract Background Atrial tachycardia (AT) is a commonly encountered rhythm disorder in patients with mitral valvular (MV) surgery. Radiofrequency (RF) ablation is the preferred therapeutic option in symptomatic patients. Purpose We aimed to evaluate the characteristics and ablation outcomes of AT in patients with previous mitral valve (MV) surgery. Methods A total of 100 symptomatic patients [mean age: 56 ±12, gender: 56 (56%) female] with documented AT were enrolled. Activation mapping was performed during tachycardia in all patients as well as entrainment mapping when needed. Voltage mapping was performed in sinus rhythm in the related atrium. Low voltage areas and signals with continuous-fragmented morphology were also tagged. Results In 127 procedures, a total of 158 ATs were documented [59 (37.3%) ATs were right-sided, 95 (60.1%) ATs were left-sided and 4(2.5%) AT was biatrial]. Mean number of ATs per procedure was 1.2±0.6. Macroreentry was the primary mechanism in right and left atrium (83.1% and 63.1%, respectively). Cavo-tricuspid isthmus (CTI) dependent macroreentry was the most frequent mechanism in right ATs whereas perimitral reentry was the most common mechanism in left ATs. Atrial low voltage zones comprised 45.5±25.1 % of total left atrium. The acute procedural success was 95.2%. Freedom from ATa after index procedure was 80% at 12 months and 65.6 % at 24 months. After multiple procedures, freedom from ATa was 77% during the mean follow-up duration of 39.7 ± 27.2 months. Conclusion Left ATs are more common compared to the right ATs and macroreentry is the major mechanism in both right & left ATs. RF ablation of ATs has favourable long-term outcomes in patients with MV surgery.

Slow pathway ablation in pediatric patients: long-term outcomes in a high-volume center according to baseline electrophysiologic characteristics

Abstract Background Slow pathway ablation (SPA) in pediatric patients with documented paroxysmal supraventricular tachycardia (PSVT) has been proven safe and effective. Arrhythmia induction is often difficult in the pediatric population. Accordingly, empirical SPA is frequently adopted in this population. Real-world data about long-term outcomes of slow pathway ablation (SPA) in relation to tachycardia inducibility and electrophysiologic characteristics in pediatric patients with PSVT in a high-volume center are lacking. Purpose To compare long-term clinical outcomes of SPA in pediatric patients with and without intraprocedural documentation of DAVP and AV nodal reentrant tachycardia induction. Methods In this retrospective sigle-center study, all SPA procedures performed on pediatric patients (under 18 years) at our Institution since 2016 were considered. All patients had documented PSVT with short RP interval, no evidet ventricular pre-excitatio on surface ECG and normal echocardiography. Baseline EPS was performed to exclude the presence of concealed accessory pathway and isoproterenol infusion was used to exclude focal atrial tachycardias. According to intraprocedural EP characteristics, three group of patients were identified: Group 1 with AVNRT induction; Group 2 with dual atrioventricular nodal physiology (DAVP) and no tachycardia induction; Group 3 without DAVP. According to previous documentation of a short RP PSVT and after discussion with patients’ families, SPA was performed in all patients. The endpoint of the ablation was to eliminate slow pathway conduction and AV node re-entrant beat. Follow up visits were scheduled three and twelve months after ablation for all patients. Results 1734 patients underwent SPA since 2016 at our Institution. 1092 patients (73.4%) showed AVNRT induction during EPS (Group 1). 433 patients (14.2%) showed DAVP without tachycardia induction (Group 2). 209 patients (12.4%) didn’t show DAVP at EPS (Group 3). Age and gender were similar among the three groups. SPA was performed with acute procedural success in all patients. After 36-month median follow-up, freedom from palpitations was 98.5% in Group 1, 97.1% in Group 2 and 92.3% in Group 3. A survival analysis showed the best outcomes in group 1 and no significant difference in recurrence rate among the groups 2 and 3 (Figure 1). No permanent heart blocks, neither other major complication was observed. Conclusions When performed by experienced operators and in high-volume centers, SPA is a safe and effective procedure in pediatric patients with documented short RP PSVT. Success rate is highest with AVNRT induction and good without AVNRT induction, regardless of AV node dual conduction at baseline EPS. Such high success rate depends on careful exclusion of others arrhythmia mechanisms (i.e., focal atrial tachycardias, AV re-entrant tachycardias) that, although infrequent in children, are the main determinants of arrhythmia recurrences.

Clinical and electrophysiological characteristics and long term outcomes of catheter ablation for right and left atrial tachycardias

Abstract Background Atrial tachycardias (AT) are complex supraventricular tachycardias which are refractory to antiarrhythmic drugs that require catheter ablation. Purpose In this trial, we aimed to evaulate the outcomes of catheter ablation in patients with symptomatic atrial tachycardia, define the acute procedural success and the recurrence rates in long-term follow-up and determine the clinical and electrophysiological features that affect these outcomes. Methods A total of 666 [mean age: 55 ±16, gender: 344 (51.7%) female] symptomatic patients with AT were enrolled. Prior catheter or surgical ablation history for ATa was present in 199 (29.9%) and 18 (2.7%) of these patients, respectively. Activation mapping was performed during tachycardia in all patients as well as entrainment mapping when needed. Voltage mapping were performed in sinus rhythm in both atriums, late potential mapping was also performed in some patients. Low voltage areas and signals with continuous-fragmented morphology were tagged. Results Macroreentry was the primary mechanism in right and left atrium (70.2% and 52.8%, respectively). Cavotricuspid isthmus (CTI) dependent macroreentry was the most frequent mechanism in right ATs and perimitral reentry and roof-dependent macroreentry were the most common mechanisms in left ATs. A total of 59 (7.5%) complications were observed in 780 procedures.(2.1% major and 5.5% minor) Acute procedural success was 95.9%. Freedom from ATa was 72.8 % during a mean follow-up of 39±23 months. Freedom from ATa after index procedure was 82.3% at 12 months and 75.9 % at 24 months. After multiple procedures, freedom from ATa was 90% at 12 months and 86% at 24 months during the follow-up. In multivariate Cox regression analysis, atrial fibrillation (AF) [(HR) 2.43, 95% c(CI) 1.78-3.30; p<0.001] , history of cardiac surgery [(HR) 1.68, 95% c(CI) 1.22-2.30; p=0.001] and moderate to severe tricuspid regurgitation [(HR) 1.47, 95% c(CI) 1.08-2.01; p=0.014] were significant predictors of ATa recurrence. Conclusion Our findings demonstrated that tailored catheter ablation of ATs especially guided by high density mapping has a high acute success rate and favourable long-term outcomes in patients with symptomatic AT episodes.

Long-term success and predictors of atrial arrhythmia recurrence following left atrial flutter ablation

Abstract Background In recent years, success rate of left atrial flutter (LAFL) ablation has witnessed improvement, attributed to enhanced comprehension of the arrhythmia mechanism and technological advancements. However, the recurrence rate and specific types of atrial arrhythmias, along with their potential predictors, remain inadequately understood. Purpose The aim of this study is to assess the factors influencing the efficacy, safety, and long-term success of radiofrequency (RF) ablation for LAFL. Methods Patients with sustained LAFL undergoing RF ablation were included in the study. LAFL mapping employed a combination of activation, voltage, and entrainment with 3D electroanatomical mapping. RF ablation targeted a protected isthmus of slow conduction, and if not localized, it involved creating lines of conduction block transecting the reentrant circuit or empirically created lines. Ablation success was defined as clean arrhythmia termination during RF application and no LAFL induction with pacing maneuvers. Follow-up included outpatient visits at 6 and 12 months. Ablation success at follow-up was defined as the absence of arrhythmia recurrence (≥30s) at regular outpatient or emergency department visits. Clinical and electrophysiological characteristics were analyzed and correlated with ablation success, complications, and freedom from arrhythmia recurrences at follow-up. Results The study included 104 consecutive patients undergoing LAFL ablation (67.5 ± 11.3 years, 67% male). Clinical characteristics comprised 12 with HFrEF, 44 with structural heart disease, 25 with valvular heart disease, 43 with previous pulmonary vein isolation (PVI) ablation, and 39 with significant left atrium enlargement. Simultaneous cavotricuspid isthmus ablation (CTI) was performed in 46 patients. LAFL cycle length was 293±68 ms, with more than one LAFL mechanism (2.0±0.8 mechanisms) demonstrated in 76 patients (73%). The most common LAFL mechanism was perimetral reentry (37%). LAFL was successfully ablated 83% of cases, with 7 patients experiencing complications (4 tamponades and 3 sinus node dysfunctions following LAFL termination). At a median follow-up of 28 months, 35 patients (34%) had AFL recurrence, and 15 of them required a second ablation procedure. No factor was associated with LAFL recurrence, except for a short LAFL cycle length (P=0.04) at the ablation procedure. Demonstration of more than one LAFL mechanism (P=0.48) or LAFL termination by focal or linear RF application (P=0.99) were not associated with AFL recurrences at follow-up. Conclusions Despite the relatively high efficacy of LAFL ablation, the rate of atrial arrhythmia recurrences at follow-up after a single procedure remains elevated, predominantly in the form of AFL rather than AF. Short LAFL cycle length at the index procedure appears to be a significant predictor of these recurrences. Arrythmia cycle length proved to be predictive factor of LAFL ablation success rate.Peri-veinal left AFL, LAT map, CranialPeri-veinal left AFL, LAT map, PA

Multimodal imaging and electrophysiological study in the differential diagnosis of rest tremor

IntroductionDistinguishing tremor-dominant Parkinson's disease (tPD) from essential tremor with rest tremor (rET) can be challenging and often requires dopamine imaging. This study aimed to differentiate between these two diseases through a machine learning (ML) approach based on rest tremor (RT) electrophysiological features and structural MRI data.MethodsWe enrolled 72 patients including 40 tPD patients and 32 rET patients, and 45 control subjects (HC). RT electrophysiological features (frequency, amplitude, and phase) were calculated using surface electromyography (sEMG). Several MRI morphometric variables (cortical thickness, surface area, cortical/subcortical volumes, roughness, and mean curvature) were extracted using Freesurfer. ML models based on a tree-based classification algorithm termed XGBoost using MRI and/or electrophysiological data were tested in distinguishing tPD from rET patients.ResultsBoth structural MRI and sEMG data showed acceptable performance in distinguishing the two patient groups. Models based on electrophysiological data performed slightly better than those based on MRI data only (mean AUC: 0.92 and 0.87, respectively; p = 0.0071). The top-performing model used a combination of sEMG features (amplitude and phase) and MRI data (cortical volumes, surface area, and mean curvature), reaching AUC: 0.97 ± 0.03 and outperforming models using separately either MRI (p = 0.0001) or EMG data (p = 0.0231). In the best model, the most important feature was the RT phase.ConclusionMachine learning models combining electrophysiological and MRI data showed great potential in distinguishing between tPD and rET patients and may serve as biomarkers to support clinicians in the differential diagnosis of rest tremor syndromes in the absence of expensive and invasive diagnostic procedures such as dopamine imaging.

Unique clinical and electrophysiological features in the peripheral nerve system in patients with sialidosis – a case series study

BackgroundTo investigate the peripheral nervous system involvement in S sialidosis with typical features of myoclonus, seizure, and giant waves in somatosensory evoked potentials suggesting hyperexcitability in the central nervous system.MethodsThe clinical presentation of patients with genetically confirmed sialidosis was recorded. Neurophysiological studies, including nerve conduction studies (NCSs), F-wave studies, and needle electromyography (EMG), were performed on these patients.ResultsSix patients (M/F: 2:4) were recruited. In addition to the classical presentation, intermittent painful paresthesia was noted in four patients, and three of whom reported it as the earliest symptom. In the NCSs, one patient had reduced compound muscle action potential amplitudes in the right ulnar nerve, while another patient had prolonged distal motor latency in the bilateral tibial and peroneal nerves. Prolonged F-wave latency (83.3%), repeater F-waves (50%), and neurogenic polyphasic waves in EMG (in 2 out of 3 examined patients) were also noted. Interestingly, a very late response was noted in the F-wave study of all patients, probably indicating lesions involving the proximal peripheral nerve or spinal cord.ConclusionIn addition to the central nervous system, the peripheral nervous system is also involved in sialidosis, with corresponding clinical symptoms. Further study on these phenomena is indicated.

Is the conventional deployment of electrode catheters appropriate to diagnose the circuit of atypical atrioventricular nodal reentrant tachycardia? -New insights into the retrograde slow pathways-

Abstract During atypical atrioventricular nodal reentrant tachycardia (AVNRT), the earliest atrial activation site following retrograde slow pathway conduction is either at the exit of the left inferior extension (LIE) in the coronary sinus (CS) or that of the right inferior extension (RIE) on the tricuspid annulus (TA). In an EP study, LIE can be detected by the CS catheter, but absence of catheters at the RIE can lead to it being missed. Aim To evaluate the electrophysiological characteristics of the retrograde slow pathway. Methods We assessed patients with atypical AVNRT using electro-anatomical 3D mapping. Results Among 14 patients (9 females, age 59±17), with a total of 18 atypical AVNRTs (15 fast/slow and 3 slow/slow), 4 patients had LIE, 6 had RIE, and 4 had both. The LIE exits were inside the CS, while those of RIE were on the posterior TA. During AVNRT or ventricular pacing, the local electrogram of RIE preceded that of the CS ostium and HBE by 24±12 and 34±12 ms respectively. Examination of activation times at the CS ostium and HBE showed that the nearer to the exit of RIE they were, the earlier they were excited. Conclusion The retrograde slow pathway of atypical AVNRT can have an exit site at the LIE or RIE, or both. Accurate identification of inferior extensions of the AV node is critical for diagnosis and treatment. We recommend placing a catheter on the posterior TA or 3D mapping the area for RIE exit detection in atypical AVNRT patients.

Characterization of conduction recovery and atrial electrophysiological properties after pulmonary vein isolation using pulsed field ablation

Abstract Background Pulsed field ablation (PFA) is a relatively new technology for isolation of pulmonary veins in patients with atrial fibrillation (AF). Data addressing reasons for recurrent atrial fibrillation despite primarily successful pulmonary vein isolation (PVI) using PFA are scarce, due to an up to date limited number of patients treated this way. Objective The aim of this study was to analyze electrophysiological characteristics of reconduction and / or left atrial substrate of patients referred to our center for Re-Do procedures for recurrent AF after an initial PVI using PFA. Methods 90 patients (mean age 66±9 years, 69 male (77%)) had been treated in our center from November 2021 to July 2023 with PVI using PFA. 9 (10%) of these patients were referred for Re-Do procedures. These were performed by radiofrequency ablation (RFA) using Carto system including high density mapping and high power / short duration (HPSD) ablation. We analyzed location of PV reconnection and low voltage areas (LVA) in the left atria. Results 7 out of 9 patients (77%) presented with reconnections of pulmonary veins. In one patient a single vein showed reconduction (RSPV), in 5 patients 2 veins were conducting (1x LSPV, 3x LIPV, 1 left sided common os (LCo), 1x RSPV, 3x RIPV). None of the patients showed 3 or 4 reconnected veins. Areas of reconduction in each vein were: LSPV 1x ridge, 1x posterior; LIPV 1x posterior, 1x anterior and posterior; LCo 1x posterior, RSPV 1x anterior, 2x carina, 1x anterior and posterior; RIPV 1x complete, 2x carina. In 7 patients a fibrotic atrial cardiomyopathy (FACM) was diagnosed via high density mapping of LVA’s. In 2 of these patients all 4 pulmonary veins were chronically isolated after the initial PVI. All patients except one (very small anterior LVA) with FACM ≥1 were treated with additional linear or encircling lesions according to the individual extent of the fibrotic areas. 2 patients had no LVA’s detectable. In one of those 2 patients 2 veins had reconnected. The other patient had chronically isolated veins (no proof of dormant conduction with adenosine) and no detectable non-PV-triggers under isoprenaline. Conclusion In the population of patients undergoing PVI using PFA in our center, only 10% had clinically relevant recurrences leading to the necessity of a Re-Do procedure. Most patients (77%) in this setting had reconnections of pulmonary veins. There is a tendency of posterior reconnections of the left pulmonary veins and reconnections of the carina of the right pulmonary veins, but the number of patients is too small to clearly define predilection sites that have to be paid attention to when using PFA. Additionally, left atrial substrate is an important problem in patients with recurrent AF despite primarily successful PVI and has to be considered and thoroughly addressed in Re-Do procedures.Reconnection of LSPV and anterior LVAAblation of RSPV and LSPV (posterior)

Electrophysiological characteristics of tachyarrhythmia and effects of catheter ablation in patients with Fontan circulation

Abstract Introduction Incidence of arrhythmia in complex congenital heart disease is higher than general population. Characteristics of arrhythmia in patients with functional single ventricle is not known. Methods Total 18 patients (age, 22.1 8.5 years, 9 men) with Fontan circulation who had undergone catheter ablation for tachyarrhythmia were retrospectively consecutively included. Characteristics of congenital heart disease, mechanisms of tachyarrhythmia, and efficacy and safety of catheter ablation were analyzed. Results Congenital heart diseases of the patients were as follows: double outlet right ventricle, 9; common atrioventricular septal defect, 5; and pulmonary atresia, 4. Fontan types were as follows: lateral tunnel Fontan, 9; extracardiac conduit Fontan 9. Fontan conduit puncture was successful in all patients. Mechanisms of tachyarrhythmia were as follows: intraatrial macroreentrant tachycardia, 8; focal atrial tachycardia, 4; atrioventricular nodal reentrant tachycardia, 3; twin atrioventricular nodal reciprocating tachycardia, 2; unknown, 2. Success rate of catheter ablation, recurrence rate, and complication rate were 16 of 18 patients, 2 of 18 patients, and 0 of 18 patients, respectively. Conclusion Intraatrial macroreentrant tachycardia is the most common tachycardia mechanism in patients with Fontan circulation. Catheter ablation for tachyarrhythmia is effective and safe in these population.

Left bundle fascicular versus left bundle trunk pacing: a comparison of their electrical synchrony parameters

Abstract Background Variation in human left bundle branch (LBB) anatomy has a significant effect on the sequence of left ventricular depolarization. However, little is known regarding the electrophysiological characteristics of pacing different LBB fascicles. Objective We aimed to analyse the different electrocardiographic characteristics of LBB pacing (LBBP) attending to the site of pacing at the LBB system. Methods In consecutive patients with confirmed LBBP, we distinguished left bundle trunk capture (LBTP) from any LB fascicular pacing (LBFP) based on the presence of LB potentials and paced QRS morphologies in the frontal axis. We compared them regarding procedure, LBBP criteria and electrical synchrony parameters. Results 309 patients with LBBAP attempt were analysed, with 290 successful cases. Among them, 223 were considered LBBP. 25 cases without a proper ECG tracing in the frontal leads were excluded from the final analysis. 173 patients with LBFP were compared to 25 patients with LBTP. There were not significant differences in the baseline characteristics, but the native QRS width was higher in the LBFP group (119.2±31.4 ms vs 103.2±20.5 ms; p=0.014). Regarding the procedural duration, there was not any significant difference. QRS transition criteria (80.0% vs 61.8%; p=0.077), selective LBBP (40.0 vs 21.5%; p=0.101), paced QRS width (110.3±16.8 ms vs 115.4±14.9 ms; p=0.117), V6-RWPT (79.2±10.7 ms vs 75.3±9.7 ms; p=0.068) and interpeak interval (42.5±19.1 ms vs 45.7±12.9 ms; p=0.282) were not significantly different between LBTP and LBFP. All short-term complications occurred in LBFP, mainly driven by septal perforations (n=23), without any difference in the pacing parameters. Among the LBFP subgroups, left septal (LSFP) and posterior (LPFP) fascicles were significantly more prevalent than left anterior (LAFP) in LBFP (46.8%, 41.0% and 12.2% respectively). Regarding the baseline characteristics, the procedural performance and the electrical synchrony parameters, there were not significant differences among the LBFP subgroups. Only aVL-RWPT was longer when the posterior fascicle was paced, and shorter in LAFP (84.7±13.3 ms vs 64.9±15.1 ms; p<0.001). The consecution of LSFP was more frequent with lumenless leads (97.5% vs 83.1% vs 81.0%, p=0.006). Attending to the LBBP criteria, transition criteria were more frequent in LSFP (71.6% vs 53.2%; p=0.039), along with selective capture (29.6% vs 16.3%%; p=0.042), and transition during pacing manoeuvres (82.8% vs 69.2% vs 40.0%; p=0.013). Conclusions LBFP is much more prevalent than LBTP in unselected consecutive patients with LBBP. LBFP seems more feasible, and as good as LBTP in terms of electrical synchrony and pacing safety, without significant differences among the LBFP subgroups. The recognition of the different paced QRS morphologies in the frontal axis, along with the analysis of the Purkinje potentials, arise as important tools to fully understand the whole map of LBBAP.Left bundle branch area sites of pacingProcedural and LBBP characteristics