Analysis Of Electrograms Research Articles

Intracardiac electrogram analysis may allow for prediction of lesion transmurality after Pulsed Field Ablation of atria in a porcine model

Intracardiac electrogram analysis may allow for prediction of lesion transmurality after Pulsed Field Ablation of atria in a porcine model

Fractional-order modeling of myocardium structure effects on atrial fibrillation electrograms

Atrial fibrillation (AF) is the most common cardiac arrhythmia with mechanisms of initiation and sustaining that are not fully understood. The clinical procedure for AF contemplates the analysis of the atrial electrograms, whose morphology has been correlated with the underlying structure of the atrial myocardium. This study employs a mathematical model incorporating fractional calculus to simulate cardiac electrical conduction, accounting for tissue structural inhomogeneities using complex-valued orders. Simulations of different wavefront propagation patterns were performed, and virtual electrograms were analyzed using an asymmetry factor. Our results evinced that the shapes of the action potential and the propagating wavefront can be modulated through the fractional order under both healthy and AF conditions. Moreover, the asymmetry factor changes with variations in the fractional order. For a given propagation pattern under AF conditions, variation intervals for the asymmetry factor can be generated by forming sets of simulations with different configurations for the fractional order, representing diverse samples of atrial tissue with varying degrees of structural heterogeneity. This approach successfully reproduces the electrogram negative deflection predominance seen in AF patients, which standard integer-order models cannot predict. Our fractional-order conduction model aligns with the effects of atrial structure on the electrical dynamics observed in clinical AF. Therefore, it offers a valuable tool for studying cardiac electrophysiology, encompassing both electrical and structural interactions of the tissue within a unified model.

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.

Stochastic time series analysis of atrial fibrillatory electrograms in paroxysmal atrial fibrillation

Abstract Background/Introduction Regional dominant frequency and instantaneous frequency modulation of short fractionated atrial electrograms have been associated with ablation targets and the prognosis of atrial fibrillation (AF). However, inconsistent and not fully comprehensible results have been reported. Purpose To construct a simple computational algorithm for the analysis of continuous fibrillatory atrial electrograms and evaluate it in clinical practice, among patients with paroxysmal AF. Methods Before the first cryo-balloon ablation, 3-minute continuous local electrogram recordings during pace-induced AF were obtained by the circumferential catheter from the left atrial appendage (LAA) and each pulmonary vein: left superior (LSPV), left inferior (LIPV), right superior (RSPV) and right inferior (RIPV). Following time- and frequency-domain analysis, non-linear detrended fluctuation analysis (DFA α) with analysis for short-term (DFA α1) and long-term fluctuations (DFA α2) was performed. The signals were detrended by subtracting time series polynomial fit and badpass filtered in the MATLAB environment (cut-off voltage 0.1 mV to avoid scar and artifacts). Results Fifteen patients were studied. Among different atrial areas, higher mean peak rate (pr) along with lower standard deviation of between peaks intervals (sdpp) and root square of peak-to-peak differences (rmppd) were observed in the LAA and left veins (Fig. 1). In patients with longer AF history (> 2 yrs), lower α, α1 and α2 exponents of DFA were observed (Fig. 2). Conclusions This algorithm depicted dissimilar impact on atrial electrical activity between different atrial areas. Patients with longer AF history had less self-similarity in local LAA electrograms. This might indicate possible ablation targets and reveal patients with greater AF burden and worse arrhythmic prognosis.Leftheriotis - Figure 1Leftheriotis - Figure 2

Cardioneuroablation for vasovagal syncope. Results from an EHRA Survey

Abstract Background Cardioneuroablation (CNA) is a recently introduced catheter-based therapy for vasovagal syncope (VVS), involving the modulation of the cardiac autonomic nervous system. Over the past decade, the body of evidence supporting CNA has consistently grown, sparking increased interest, and leading to broader adoption of this novel therapy for VVS treatment. However, several knowledge gaps persist, particularly concerning clinical indications, methodology, and long-term outcomes. Purpose The aim of this survey is to provide a comprehensive overview of the daily utilization of CNA in Europe. Methods and Results Among 204 participants, half reported that they are already performing CNA in their centres. The survey indicated CNA as an emerging therapy, with most centres initiating this treatment within the last two years. A significant majority of those who responded (71%) adopted a systematic approach by targeting ganglionated plexuses (GPs) in both the right atrium (RA) and left atrium (LA) as their first-line approach. The second most common approach (16%) involved performing ablation LA GPs only in the cases where there is no response following RA ablation. Figure 1 shows the GPs usually targeted for ablation. The most frequent procedural endpoint was the increase in the heart rate. Ninety percent of respondents relied on an anatomical approach for GP localization, while 59% also guided the procedure using electrogram analysis. Less frequently used approaches included pre-procedural imaging (20%), high-frequency stimulation (17%), and spectral analysis (10%). Only 11% of physicians discharged patients who underwent CNA without anticoagulation or antiplatelet therapy. In most cases (58%), respondents discharged their patients with anticoagulation, while 28% on single antiplatelet therapy. Overall, CNA is considered an effective procedure (80% of responders rating its effectiveness at or above 70%) and a safe procedure (with an estimated 1% rate of procedure-related complications, with symptomatic sinus tachycardia being the most frequently reported). Conclusions This survey confirmed high expectations for the future of this therapy, as most responders anticipate that CNA will be indicated as a first-line therapy for patients with recurrent cardioinhibitory VVS. Future efforts are necessary to standardize the procedural flow and peri-procedural patient management.

Predictors of decremental conduction after extrastimulus in post-infarction ventricular tachycardia substrate maps

Abstract Introduction Ventricular tachycardia (VT) substrate ablation techniques attempt to identify areas of decremental conduction (DC) within the scar, given their close relationship with VT isthmuses. DC identification requires the systematic use of extrastimuli during substrate mapping. This can be time consuming and induce ventricular arrhythmias during mapping. Objective This study aims to identify predictors of decremental response after extastimulus that allow recognizing areas with higher probability of DC conduction in order to focus functional mapping of the substrate on them. Methods Sixteen consecutive ischemic patients (93.8% male, 66.3±12.4 years) undergoing VT substrate ablation were included. A detailed substrate map during right ventricular (RV) pacing was obtained in all of them. Systematic analysis of electrograms (EGMs) recorded from the infarct area was performed during RV pacing at 600-500 ms, and during a short-coupled RV extrastimulus. Electrograms during RV pacing exhibiting decremental evoked conduction delay after an extrastimulus (DECD-AE) were compared to those not showing DECD-AE. Results Mean low voltage (<1.5 mV) area was 45±18.6 cm2. A total of 1744 EGMs were analyzed. Of them, 453 (26%) showed DECD-AE. Bipolar EGMs showing DECD-AE exhibited a higher number of deflections [4(interquartile range 3-5) vs 2(1-3); p<0.0001], a higher amplitude [0.52(0.27-1) vs 0.3(0.14-0.7) mV; p=0.003] and similar duration [114(102-135) vs 117(100-133 ms); p=0.492] compared to EGMs without DECD-AE. The area under curve was 0.64 for bipolar voltage and 0.8 for number of bipolar deflections. The presence of <3 bipolar deflections excluded DECD-AE with a negative predictive value of 98.5%. Conclusions In areas of myocardial scar, bipolar EGMs with <3 deflections are unlikely to present DECD-AE. Focusing functional mapping on signals with ≥3 deflections could simplify procedures and save time.

Changes in local endocardial electrograms immediately after PFA show dose-dependent variations

Abstract Background/Introduction Pulsed field ablation (PFA) is a novel nonthermal cardiac ablation technology based on irreversible electroporation. The behaviour of local electrograms after PFA has been poorly characterized and it remains unknown if it is possible to differentiate between different electroporation levels based on local electrogram analysis. Purpose The objective of this study was to characterize the alterations in bipolar and unipolar endocardial electrograms after performing PFA at different doses. Methods Five anesthetized pigs were submitted to PFA treatments. Endovascular access to the right atrium was gained through the femoral vein to create a line of ablation between the superior and inferior vena cava using a focal monopolar catheter. The catheter was switched between a conventional cardiac navigation system (CARTO system) and a custom PFA generator. Two different PFA doses were used: a high dose (HD-1600V) at top and bottom of the line and a low dose (LD-1000V) in the central part of the ablation line. Bipolar and unipolar electrograms were recorded with the ablation catheter before and immediately after each ablation. Additionally, high-density electroanatomical maps were acquired with a multielectrode catheter before and immediately after the procedures. Four weeks later, the animals were remapped again and subsequently euthanized. Atrial tissue was removed and processed to identify the presence of fibrosis in the previously ablated lesions. Results We performed 106 ablations (84 high dose vs. 22 low dose). Four weeks later, histological staining of chronic lesions revealed that the HD lesions were larger and more fibrotic than the LD (Figure 1). Immediately after each ablation R/S-wave amplitudes and their corresponding |dV/dt|max decreased for the bipolar and unipolar electrograms. The percentages of bipolar electrogram reduction HD vs. LD were: R wave 73% vs. 39%, S wave 68% vs. 37% and |dV/dt|max 81% vs. 38%; 1 way-ANOVA p<0.05 for all, Figure 2). The R-wave amplitude in M1-M2 was significantly lower in HD compared to LD (HD vs. LD: 0.3 ± 0.2 mV vs. 0.7 ± 0.6 mV; 1 way-ANOVA p<0.01). S-wave and |dV/dt|max of unipolar electrograms presented a similar behaviour (M2 |dV/dt|max HD vs. LD: -116 ± 118 mV/s vs. -260 ± 267 mV; 1 way-ANOVA p<0.01). Conclusion Local electrograms display PFA dose-dependent variations. This information could result useful to create new metrics to assess in real time the performance of PFA systems.Figure 1.EAM maps and histology studyFigure 2.EGM signals and statistics

Systematic in-silico evaluation of fibrosis effects on re-entrant wave dynamics in atrial tissue.

Despite the key role of fibrosis in atrial fibrillation (AF), the effects of different spatial distributions and textures of fibrosis on wave propagation mechanisms in AF are not fully understood. To clarify these aspects, we performed a systematic computational study to assess fibrosis effects on the characteristics and stability of re-entrant waves in electrically-remodelled atrial tissues. A stochastic algorithm, which generated fibrotic distributions with controlled overall amount, average size, and orientation of fibrosis elements, was implemented on a monolayer spheric atrial model. 245 simulations were run at changing fibrosis parameters. The emerging propagation patterns were quantified in terms of rate, regularity, and coupling by frequency-domain analysis of correspondent synthetic bipolar electrograms. At the increase of fibrosis amount, the rate of reentrant waves significantly decreased and higher levels of regularity and coupling were observed (p < 0.0001). Higher spatial variability and pattern stochasticity over repetitions was observed for larger amount of fibrosis, especially in the presence of patchy and compact fibrosis. Overall, propagation slowing and organization led to higher stability of re-entrant waves. These results strengthen the evidence that the amount and spatial distribution of fibrosis concur in dictating re-entry dynamics in remodeled tissue and represent key factors in AF maintenance.

Cardioneuroablation for vasovagal syncope: insights on patients' selection, centre settings, procedural workflow and endpoints-results from an European Heart Rhythm Association survey.

Cardioneuroablation (CNA) is a catheter-based intervention for recurrent vasovagal syncope (VVS) that consists in the modulation of the parasympathetic cardiac autonomic nervous system. This survey aims to provide a comprehensive overview of current CNA utilization in Europe. A total of 202 participants from 40 different countries replied to the survey. Half of the respondents have performed a CNA during the last 12 months, reflecting that it is considered a treatment option of a subset of patients. Seventy-one per cent of respondents adopt an approach targeting ganglionated plexuses (GPs) systematically in both the right atrium (RA) and left atrium (LA). The second most common strategy (16%) involves LA GP ablation only after no response following RA ablation. The procedural endpoint is frequently an increase in heart rate. Ganglionated plexus localization predominantly relies on an anatomical approach (90%) and electrogram analysis (59%). Less utilized methods include pre-procedural imaging (20%), high-frequency stimulation (17%), and spectral analysis (10%). Post-CNA, anticoagulation or antiplatelet therapy is prescribed, with only 11% of the respondents discharging patients without such medication. Cardioneuroablation is perceived as effective (80% of respondents) and safe (71% estimated <1% rate of procedure-related complications). Half view CNA emerging as a first-line therapy in the near future. This survey offers a snapshot of the current implementation of CNA in Europe. The results show high expectations for the future of CNA, but important heterogeneity exists regarding indications, procedural workflow, and endpoints of CNA. Ongoing efforts are essential to standardize procedural protocols and peri-procedural patient management.

A novel pulsed field ablation system using linear and spiral ablation catheters can create large and durable endocardial and epicardial ventricular lesions in vivo.

We investigated the preclinical safety and efficacy of ventricular pulsed field ablation (PFA) using a family of novel, 6-/8-Fr, linear, and spiral PFA/mapping catheters (CRC EP, Inc). QRS-gated, bipolar PFA (>2.0 kV) was performed in 10 healthy swine. Altogether, 20 endocardial and epicardial right and left ventricular applications were delivered. The catheters were inserted through an 8.5-Fr steerable introducer. The intensity of skeletal muscle activation was quantified using an accelerometer. Lesions were assessed by pre- versus post-PFA electrogram analysis, pacing threshold, 3D voltage mapping, necropsy, and histology. The swine rete mirabile, liver and kidneys were examined for embolic events. All applications were single-shot (56 ± 18 s) without catheter repositioning. Minimal microbubbling was observed without significant skeletal muscle stimulation (mean acceleration 0.05 m/s2) or ventricular tachyarrhythmias. There was significant reduction in post- versus pre-PFA electrogram amplitude (0.5 ± 0.2 mV versus 3.2 ± 0.9 mV, P < 0.001) with a marked increase in pacing threshold (>20 mA versus 7.5 ± 2.9 mA, P < 0.001). All lesions were large and durable up to 28 days, measuring 32 ± 5 mm (length), 27 ± 8 mm (width), and 8 ± 3 mm (depth) using the spiral catheters and 43 ± 1 mm (length), 7 ± 1 mm (width), and 8 ± 1 mm (depth) using the linear catheters. Despite higher waveform voltages and prolonged applications, no thermal effects were detected at necropsy/histology. Moreover, gross and microscopic examinations revealed no evidence of thromboembolism, vascular or collateral injury. A novel, QRS-gated PFA system using linear and spiral PFA catheters is capable of creating large and durable ventricular lesions in vivo without significant microbubbling, ventricular arrhythmias or thromboembolism.

Comparison of electrogram characteristics in persistent atrial fibrillation.

Multiple analysis techniques evaluate electrograms during atrial fibrillation (AF), but none have been established to guide catheter ablation. This study compares electrogram properties recorded from multiple right (RA) and left atrial (LA) sites. Multisite LA/RA mapping (281 ± 176/239 ± 166 sites/patient) was performed in 42 patients (30 males, age 63 ± 9 years) undergoing first (n = 32) or redo-AF ablation (n = 10). All electrogram recordings were visually reviewed and artifactual signals were excluded leaving a total of 21 846 for analysis. Electrogram characteristics evaluated werecycle length (CL), amplitude, Shannon's entropy (ShEn), fractionation interval, dominant frequency, organizational index, and cycle length of most recurrent morphology (CLR ) from morphology recurrence plot analysis. Electrogram characteristics were correlated to each other. All pairwise comparisons were significant (p < .001) except for dominant frequency and CLR (p = .59), and amplitude and dominant frequency (p = .38). Only ShEn and fractionation interval demonstrated a strong negative correlation (r = -.94). All other pairwise comparisons were poor to moderately correlated. The relationships are highly conserved among patients, in the RA versus LA, and in those undergoing initial versus redo ablations. Antiarrhythmic drug therapy did not have a significant effect on electrogram characteristics, except minimum ShEn. Electrogram characteristics associated with ablation outcome were shorter minimum CLR , lower minimum ShEn, and longer mimimum CL. There was minimal overlap between the top 10 sites identified by one electrogram characteristic and the top 10 sites identified by the other 10 characteristics. Multiple techniques can be employed for electrogram analysis in AF. In this analysis of eightdifferent electrogram characteristics, seven were poorly to moderately correlated and do not identify similar locations. Only some characteristics were predictive of ablation outcome. Further studies to consider electrogram properties, perhaps in combination, for categorizing and/or mapping AF are warranted.

Predictors of single shot pulmonary vein isolation with Heliostar radiofrequency balloon

Abstract Introduction Single shot pulmonary vein isolation techniques have emerged as an effective and safe alternative to point-by-point ablation, considerably reducing procedure times. The recent appearance on the market of the Heliostar® radiofrequency (RF) balloon offers a new option in this regard. The main predictors of single-shot isolation with this new device are unknown. Objectives Our objective was to evaluate as potential predictors of single-shot isolation the impedance drop, temperature rise and voltage reduction of the electrograms recorded by the balloon during radiofrequency application. Methods A total of 25 patients with paroxysmal (68%) or persistent (32%) symptomatic atrial fibrillation were prospectively included and underwent pulmonary vein isolation with Heliostar® RF balloon. Impedance and temperature parameters were collected from each of the applications performed in all veins. The voltage of the electrograms recorded by the Heliostar® RF balloon immediately before and after initiating the RF application in each vein was collected. The number of applications per vein was recorded and the single shot criterion was discriminated in each vein. A total of 92 veins were included for impedance and temperature analysis, and 59 veins for electrogram analysis (excluding veins in which the RF application was performed in atrial fibrillation). Impedance drop, temperature increase and electrogram voltage decrease during each application were analysed by logistic regression to correlate these parameters as potential predictors of single shot isolation. Results Single shot isolation was obtained in 64.1% of the veins. Applications that obtained persistent single shot isolation showed a higher impedance drop [22.5 ± 6.3 Ω vs 19 ± 5.3 Ω, p = 0.005] and a higher temperature rise [12.5 ± 4.4 ºC vs 10.3 ± 3.5 ºC, p = 0.008]. The voltage reduction of the electrograms collected by the balloon, on the other hand, did not differ significantly between the two groups [2.3 mV in single shot vs 2.2 mV in non-single shot applications, p = 0.4]. Univariate analysis by logistic regression showed impedance drop [OR per 1 Ω increase, 1.11, 95% CI 1.02-1.21, p = 0.007] and temperature increase [OR per 1°C increase, 1.15, 95% CI 1.02-1.3, p = 0.01] as significant predictors of single shot isolation. Conclusions Impedance drop and temperature rise during application were significant predictors of single shot isolation with Heliostar® RF balloon. The voltage reduction of the electrograms recorded by the balloon was not a predictor of single shot application.

Dynamics of High-Density Unipolar Epicardial Electrograms During PFA.

Pulsed field ablation (PFA) is a novel nonthermal cardiac ablation technology based on irreversible electroporation (IRE). While areas of IRE lead to durable lesions, the surrounding regions, where reversible electroporation occurs, recover. The behavior of local electrograms in areas of different electroporation levels remains unknown. The goal of this study is to characterize electrogram dynamics after PFA in IRE and reversible electroporation areas. A total of 6 domestic swine were used. PFA was applied in the epicardium of the right and left ventricles using a focal monopolar catheter. Additional radiofrequency ablations were performed. Epicardial unipolar electrograms were acquired at baseline and for 60 minutes post PFA/radiofrequency ablation using a high-density electrode matrix attached to the epicardium. Electrogram dynamics were analyzed in areas corresponding to different levels of electroporation. Acute lesion formation was assessed after 3 to 5 hours by triphenyl tetrazolium chloride staining. Electrogram analysis demonstrated a clear association between electrogram changes and the level of electroporation. Immediately after PFA, electrograms displayed the following: a significant decrease in R/S-wave amplitude; a large elevation of the ST-segment; and a large decrease in their |(dV/dt)|max. Marked changes in electrograms were observed beyond the lesion area. Thereafter, a gradual recovery was observed. The evolution of all the electrogram parameters throughout the 60 minutes after PFA was significantly different (P<0.05) between the IRE and reversible electroporation areas. Acute lesion staining showed significantly larger depth for PFA lesions compared with radiofrequency ablation. This study shows that unipolar electrograms can differentiate between reversible electroporation and IRE areas during the first 30 minutes post ablation. Differences after the first 30 minutes are less evident. Our findings could result useful for immediate lesion assessment after PFA and warrant further investigation.

Focal activity in atrial fibrillation: state of the art

Focal activity is one of the dominant triggers of atrial fibrillation. Its activity is revealed in paroxysmal as well as in persistent patterns of arrhythmia. Starting as a trigger of atrial fibrillation in pulmonary veins, over time with increasing of burden of atrial fibrillation, focal activity is more and more revealed out of pulmonary veins: anterior and posterior left atrial walls, interatrial septum, coronary sinus, ligament of Marshal and right atrium. Diagnostics of focal activity is a challenging clinical task despite implementation of mathematical algorithms of electrogram analysis because of its spatial instability and activation direction of the mapping electrode. All these items are discussed in the article.

Distributions and number of drivers on real-time phase mapping associated with successful atrial fibrillation termination during catheter ablation for non-paroxysmal atrial fibrillation.

Real-time phase mapping (ExTRa™) is useful in determining the strategy of catheter ablation for non-paroxysmal atrial fibrillation (AF). This study aimed to investigate the features of drivers of AF associated with its termination during ablation. Thirty-six patients who underwent catheter ablation for non-paroxysmal AF using online real-time phase mapping (ExTRa™) were enrolled. A significant AF driver was defined as an area with a non-passively activated ratio of ≥ 50% on mapping analysis in the left atrium (LA). All drivers were simultaneously evaluated using a low-voltage area, complex fractionated atrial electrogram (CFAE), and rotational activity by unipolar electrogram analysis. The electrical characteristics of drivers were compared between patients with and without AF termination during the procedure. Twelve patients achieved AF termination during the procedure. The total number of drivers detected on the mapping was significantly lower (4.4 ± 1.6 vs. 7.4 ± 3.8, p = 0.007), and the drivers were more concentrated in limited LA regions (2.8 ± 0.9 vs. 3.9 ± 1.4, p = 0.009) in the termination group than in the non-termination group. The presence of drivers 2-6 with limited (≤ 3) LA regions showed a tenfold increase in the likelihood of AF termination, with 83% specificity and 67% sensitivity. Among 231 AF drivers, the drivers related to termination exhibited a greater overlap of CFAE (56.8 ± 34.1% vs. 39.5 ± 30.4%, p = 0.004) than the non-related drivers. The termination group showed a trend toward a lower recurrence rate after ablation (p = 0.163). Rotors responsible for AF maintenance may be characterized in cases with concentrated regions and fewer drivers on mapping.

Detection of the most dominant drivers of atrial fibrillation based on repetitive activity in sequential electro-anatomical mapping

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This work is part of Personalize AF. This project received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860974, This work was also supported by the Swiss National Supercomputing Centre (CSCS), project s1074. Introduction Detecting and targeting the most dominant drivers of atrial fibrillation (AF) might improve the outcome of AF ablation procedures. We hypothesize that dominant drivers entrain their vicinity in a temporally and spatially stable manner resulting in local as well as adjacent repetitive activation patterns. Purpose We present a novel approach to detect the most dominant drivers of AF based on driver repetitiveness and the degree to which they entrain their vicinity. Methods We retrospectively analyzed a dataset of high-density bi-atrial sequential mapping in ablation-naive persistent AF patients (n=13, 30s recording per site). Candidate drivers (focal activity or re-entry) were detected based on local activation time analysis of unipolar electrograms. Focal activity was defined as radial spread of activation, re-entry as a circular activation sequence on at least 4 splines of the mapping catheter that covered &amp;gt;50% of the AF cycle length. As a measure of driver stability, we determined the driver's local repetitiveness (in % of recording). As a measure of driver-associated entrainment, we determined the directionally coherent repetitiveness of adjacent recordings within 30 mm (Figure 1). Following our hypothesis, most dominant drivers can be recognized by their high local and directional coherent adjacent repetitiveness. Results A total of 459 recordings were analyzed (35±5 per patient). We detected 130 focal activities (10±3 per patient) and 42 re-entries (4±2 per patient) in total. The spatial distribution of all drivers is shown in Figure 2 (blue bars). Focal activities were more repetitive than re-entries (Figure 2, median [IQR] 3.2% [1.9%, 5.6%] vs. 1.8% [1.8%, 2.2%], p&amp;lt;0.001 Mann-Whitney U-test). When applying a 90th percentile threshold (8.2%) to both the local and directional coherent adjacent repetitiveness to detect the most dominant drivers, we were able to detect 9 dominant drivers (all focal activities, 7 patients). Most dominant drivers were located in the upper right atrium or left pulmonary vein region (Figure 2). Interestingly, only 9 of the 130 initially detected drivers (7%) showed an activation pattern in line with a repetitive entrainment of their vicinity. Furthermore, in 6 patients (46%), no dominant drivers were detected. This might indicate that not all patients have temporally and spatially stable drivers. Conclusion In this abstract we present a novel methodology to detect the most dominant drivers of AF. Using this method, we found that some (but not all) patients have temporally and spatially stable drivers that are able to entrain their vicinity.

AB-452675-3 CHARACTERISTICS OF RESIDUAL SIGNALS AFTER PULSED FIELD ABLATION OF THE PULMONARY VEINS

Pulsed field ablation (PFA) is a new energy source for isolation of the pulmonary veins in the treatment of paroxysmal atrial fibrillation (PAF). Dose titration is challenging but important to avoid reversible electroporation. Analysis of high resolution unipolar electrograms after PFA might be of value to analyze the tissue response to PFA deliveries. Unipolar and bipolar electrograms were recorded from a proprietary pentaspline basket catheter (Boston Scientific Inc., USA) before and after PFA energy delivery using a novel electrophysiology recording system (ECGenius System, CathVision, Denmark) with resolution at a 0.05 mV level and a sampling rate of 2 KHz. Data was recorded from 12 consecutive patients diagnosed with PAF and scheduled for pulmonary vein isolation. The treatment protocol consisted of conventional PFA delivery in two baskets and two flower positions for each vein. Both unipolar and bipolar signals were analyzed manually. Overall, 790 EGMs from 12 patients were analyzed. In 131 out of 160 EGMs (82%) recorded after first PFA delivery, we observed a residual sharp downward deflection in the unipolar signal that matched the timing of the corresponding bipolar signal (Fig. 1). Median amplitude of the deflection was 0.18 mV (IQR = 0.09 - 0.32 mV). The sharp deflections were eliminated with further PFA delivery in 29.7% of cases (suggesting true local activation) but persisted in 71.3%. High resolution electrogram recording allows identification of residual sharp deflections in the unipolar electrogram after PFA delivery. The coincident timing with the bipolar EGM together with elimination by further PFA suggests that this EGM signature reflects true local activity. It remains to be seen whether persisting deflections are a measure for non-isolation or reversible electroporation.

Differences in Electrical Delay Between the Mid-septum and Apex with the Right Ventricular Lead: Novel Implications for Pacemaker Sensing.

Ventricular sensing relies on the analysis of a local intracardiac electrogram in reference to the QRS on the surface electrocardiogram. If both signals do not coincide in time, there is a delay in sensing intrinsic ventricular activity. We evaluated possible differences in the electrical delay between the mid-septum and apex as determined by the right ventricular (RV) lead position using a pacing system analyzer (PSA) during conventional pacemaker implantation. Patients without significant heart disease and intrinsic atrioventricular conduction underwent their first Medtronic (Minneapolis, MN, USA) or Abbott (Chicago, IL, USA) dual-chamber pacemaker implantation with the RV lead first positioned at the apex and then subsequently at the mid-septum. Real-time ventricular sensing data were obtained through PSA to determine the electrical delay Q-VS value as the time difference between the QRS and the released RV-sensed event marker "VS." Among 212 patients, 139 had narrow QRS and 73 had complete right bundle branch block (RBBB). Overall, both narrow QRS and RBBB patients exhibited shorter Q-VS lengths at the mid-septum compared to the apex (50.4 ± 24.2 ms and 66.7 ± 32.3 ms vs. 63.9 ± 27.6 ms and 71.7 ± 32.2 ms; P < .0001 and P < .001, respectively). The Q-VS in patients with Abbott devices was significantly shorter compared to that in patients with Medtronic devices at both the mid-septum and the apex in both patient groups (P < .0001). In conclusion, RV lead positioning at the mid-septum is associated with a shorter electrical delay compared to positioning at the apex in both narrow QRS and RBBB patients.

A Data-Driven Preprocessing Framework for Atrial Fibrillation Intracardiac Electrocardiogram Analysis

Atrial Fibrillation (AF) is the most common cardiac arrhythmia. Signal-processing approaches are widely used for the analysis of intracardiac electrograms (iEGMs), which are collected during catheter ablation from patients with AF. In order to identify possible targets for ablation therapy, dominant frequency (DF) is widely used and incorporated in electroanatomical mapping systems. Recently, a more robust measure, multiscale frequency (MSF), for iEGM data analysis was adopted and validated. However, before completing any iEGM analysis, a suitable bandpass (BP) filter must be applied to remove noise. Currently, no clear guidelines for BP filter characteristics exist. The lower bound of the BP filter is usually set to 3-5 Hz, while the upper bound (BP¯th) of the BP filter varies from 15 Hz to 50 Hz according to many researchers. This large range of BP¯th subsequently affects the efficiency of further analysis. In this paper, we aimed to develop a data-driven preprocessing framework for iEGM analysis, and validate it based on DF and MSF techniques. To achieve this goal, we optimized the BP¯th using a data-driven approach (DBSCAN clustering) and demonstrated the effects of different BP¯th on subsequent DF and MSF analysis of clinically recorded iEGMs from patients with AF. Our results demonstrated that our preprocessing framework with BP¯th = 15 Hz has the best performance in terms of the highest Dunn index. We further demonstrated that the removal of noisy and contact-loss leads is necessary for performing correct data iEGMs data analysis.

Frequency Domain Analysis of Endocardial Electrograms for Detection of Nontransmural Myocardial Fibrosis in Nonischemic Cardiomyopathy

BackgroundVoltage mapping in nonischemic cardiomyopathy can fail to identify midmyocardial substrate for ventricular arrhythmias, an important cause of ablation failure. ObjectivesThe aim of this study was to assess whether frequency domain analysis of endocardial left ventricular electrograms (EGMs) can better predict the presence of midmyocardial fibrosis (MMF) compared with voltage amplitude. MethodsNonischemic cardiomyopathy patients undergoing ventricular tachycardia ablation with registered preprocedural cardiac computed tomography and late iodine enhancement were included. Presence of fibrosis at each EGM site was assessed. Bipolar and unipolar EGMs were transformed to the frequency domain using multitaper spectral analysis. Singular value decomposition of the EGM frequency spectrum was used within a supervised machine learning process to select features to predict the presence of MMF and compare against predictions using voltage amplitude. ResultsThirteen patients were included (median age 57 years [IQR: 28-73 years], median ejection fraction 40% [IQR: 15%-57%]). A total of 6,015 EGM pairs were processed: 2,459 EGM pairs in MMF areas and 3,556 EGM pairs in non-MMF areas. Supervised classifiers were trained with stratified k-fold cross-validation within patients. The distribution of mean area under the curve metrics using frequency features, f, was significantly greater than voltage feature area under the curve metrics, v, (mean f = 0.841 [95% CI: 0.789-0.884] vs mean v = 0.591 [95% CI: 0.530-0.658]; P < 0.001), indicating that frequency-trained classifiers better predicted the presence of MMF. ConclusionsThese data indicate the promising discriminatory value of endocardial EGM frequency content in the assessment of concealed myocardial substrate. Further studies are needed to investigate the importance of the specific frequency features identified.