Local Conduction Velocity Research Articles

Identification of Critical Slowing of Conduction Using Unipolar Atrial Voltage and Fractionation Mapping

BackgroundAblation strategies targeting fractionated or low-voltage potentials have been widely used in patients with persistent types of atrial fibrillation (AF). However, recent studies have questioned their role in effectively representing sites of conduction slowing, and thus arrhythmogenic substrates. ObjectivesThe authors studied the relationship between local conduction velocity (CV) and the occurrence of fractionated and/or low-voltage potentials in order to identify areas with critically slowing of conduction. MethodsIntraoperative epicardial mapping was performed during sinus rhythm. Unipolar potentials with an amplitude <1.0 mV were initially classified as low-voltage and potentials with ≥3 deflections as fractionation. A range of thresholds were also explored. Local CV was computed using discrete velocity vectors. ResultsA total of 319 patients were included. Fractionated, low-voltage potentials were rare, accounting for only 0.36% (Q1-Q3: 0.15%-0.78%) of all atrial sites. Local CV at sites with fractionated, low-voltage potentials (46.0 cm/s [Q1-Q3: 22.6-72.7 cm/s]) was lowest compared with sites with either low-voltage, nonfractionated potentials (64.5 cm/s [Q1-Q3: 34.8-99.4 cm/s]) or fractionated, high-voltage potentials (65.9 cm/s [Q1-Q3: 41.7-92.8 cm/s]; P < 0.001). Slow conduction areas (CV <50 cm/s) could be most accurately identified by using a low voltage threshold (<1 mV) and a minimum of 3 deflections (positive predictive value: 54.2%-70.7%), although the overall sensitivity remained low (0.1%-1.9%). ConclusionsSites with fractionated, low-voltage potentials have substantially slower local CV compared with sites with either low-voltage, nonfractionated potentials or fractionated, high-voltage potentials. However, the strong inverse relationship between the positive predictive value and sensitivity of a combined voltage and fractionation threshold for slowed conduction is likely to complicate the use of these signal-based ablation approaches in AF patients.

Spatial relationship between left peri-atrial fat with underlying arrhythmogenic substrate in patients with atrial fibrillation - innocent bystander or culprit?

Abstract Introduction Peri-atrial fat may have pro-inflammatory and pro-fibrotic effects on atrial myocardium and increase the risk of developing atrial fibrillation. Consistent with prior evidence, we have previously shown that peri-atrial fat volume, but not fat attenuation (an imaging biomarker of inflammation), was associated with prevalent atrial fibrillation. Whether this association is secondary to "outside-to-inside" tissue cross talk with local adverse electrical remodelling of adjacent atrial cardiomyocytes is not known. Purpose In this novel proof of concept study, we aimed to identify a spatial relationship between left peri-atrial fat and potentially arrhythmogenic substrate (low voltage areas and slow conduction pathways) in the left atrial myocardium. Methods Contrast-enhanced cardiac computed tomography (CT) imaging and electroanatomic mapping, during coronary sinus pacing, were performed pre-ablation in atrial fibrillation patients (n=27). The left atrium and surrounding peri-atrial fat were segmented and quantified using seg3D2 and CEMRGapp. We performed registration of the electroanatomic map onto the CT-derived left atrial mesh using OpenEP and EP Workbench. Mean fat volume and attenuation around each electroanatomic point (within a 3mm radial region of interest) were correlated with local voltage and conduction velocity. Results A total of 24,839 electroanatomic points were registered onto the 3D CT-derived left atrial mesh, with a median of 935 points (range 673 to 1150) per patient. The average bipolar voltage and conduction velocity in the left atrium was 1.92±1.91 mV and 0.66±0.47 ms-1 respectively. In comparison to areas with little/no surrounding periatrial fat (Quartile 1, ≤0.93 mm3 fat per electroanatomic point), areas with the highest burden of fat (Quartile 4, ≥17.6 mm3) had significantly lower bipolar voltage (1.69±1.7 vs 2.09±2.0 mV, p&amp;lt;0.001) and conduction velocity (0.627±0.43 vs 0.700±0.47 ms-1, p&amp;lt;0.001). However, the overall correlation between periatrial fat volume with bipolar voltage (r=-0.06, p&amp;lt;0.001) and conduction velocity (r=-0.07, p&amp;lt;0.001) was weak. High, not low, fat attenuation (Quartile 4; &amp;gt;-46.5HU vs Quartile 1; ≤-75.5HU) was associated with increased bipolar voltage (2.23±2.1 vs 1.63±1.6 mV) and conduction velocity (0.703±0.42 vs 0.623±0.39 ms-1 respectively). Conclusion There is a weak correlation between periatrial fat and localized adverse electrical remodelling. The relationship between fat attenuation and electrophysiological properties was inverted. These findings confirm an association between peri-atrial fat burden but call question as to whether peri-atrial fat inflammation is implicated in atrial fibrillation pathogenesis.

Non-invasive assessment of the ventricular tachycardia isthmus during sinus rhythm

Abstract Background The ablation of ventricular tachycardias (VT) presents significant challenges due to the complex and time-consuming approaches involved in identifying arrhythmogenic regions. Combining non-invasive electrocardiographic imaging (ECGI) with endocardial mapping could potentially enhance the efficacy of interventions. Objective To evaluate the capability of ECGI in guiding operators towards areas of VT isthmuses during sinus rhythm. Methods Patients with scar-related VT, confirmed by late gadolinium enhancement cardiac magnetic resonance, were prospectively enrolled. We compared the areas of slowed conduction identified by ECGI with the VT sustaining regions identified endocardially. Simultaneous Electroanatomical Mapping (EAM) and ECGI mapping were performed during VT ablation procedures. In patients in whom a hemodynamically stable VT was maintained, the reentry circuit was mapped endocardially, and the ablation target was identified. The left ventricle was segmented into 9 regions, categorized as either VT-isthmus or non-VT isthmus based on EAM findings. Prior to ablation, local activation times (LAT) and conduction velocity (CV) ECGI sinus maps were computed. Slow conduction was quantified non-invasively by computing different ECGI metrics per region, including the mean and the standard deviation (SD) of LAT and CV, the regional Total Activation Time (rTAT) – time span between the earliest and latest activated nodes–, and the Slow Conduction Velocity (SCV) – the percentage of nodes where velocity falls below 60 cm/s -. Results The study included 20 consecutive patients with ischemic cardiomyopathy who were referred for VT ablation. A total of 21 regions linked to the VT isthmus were identified endocardially in 17 patients (age: 66.1±8.8 years, 94.1% male, left ventricular ejection fraction: 26.4±7.3%). Figure 1 illustrates the correlation between the VT circuit and the ECGI sinus map in two patients with extensive left ventricular fibrosis. ECGI metrics related to VT isthmuses exhibited a higher standard deviation in both LAT (18.1±2.0 vs 9.8±1.2 ms; p=0.001), and CV (50.4±4.7 vs 37.1±2.8 cm/s; p=0.011), and a greater percentage of nodes with slowed conduction (13.7±2.7 vs 7.4±1.6 %; p=0.029), compared to non-VT isthmus regions, Figure 2. Multivariate logistic regression analysis revealed that SD-LAT was the strongest predictor of VT isthmus localization. Conclusion ECGI has demonstrated the capability to pinpoint slowed conduction areas responsible for VT in sinus rhythm, showing promise in planning and guiding VT ablation strategies. This advancement paves the way for further research into using this non-invasive tool to improve risk stratification methods for ventricular arrhythmias.

Conduction velocity mapping in atrial fibrillation using omnipolar technology.

Recent studies have shown that atrial slow conduction velocity (CV) is associated with the perpetuation of atrial fibrillation (AF). However, the criteria of CV measurement have not been standardized. The aim of this study was to evaluate the relationship between the slow CV area (SCVA) measured by novel omnipolar technology (OT) and AF recurrence. This study included 90 patients with AF who underwent initial pulmonary vein isolation (PVI). The segmented surface area of the SCVA was measured by left atrial (LA) electrophysiological mapping using OT before the PVI. The proportion of the SCVA at each cutoff value of CV (from<0.6to<0.9m/s) was compared between the patients with and without AF recurrence. During a mean follow-up period of 516±197 days, the recurrence of AF after the initial PVI was observed in 23 (25.5%) patients. In patients with AF recurrence, the proportion of the SCVA in the LA posterior, LA appendage (LAA), and LA anterior were significantly higher than those without AF recurrence. The multivariate analysis indicated that the proportion of the low voltage area and the SCVA in the LA anterior (local CV<0.7m/s) were independent predictors of AF recurrence (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.01-1.14; p=0.03; HR, 1.40; 95% CI, 1.07-1.83; p=0.01, respectively). By evaluating the local CV using OT, it was indicated that SCVA with CV<0.7m/s in the LA anterior is strongly associated with AF recurrence after PVI.

Local changes in conduction velocity in the left atrium of atrial fibrillation patients undergoing pulmonary vein isolation

Abstract Background Electro-anatomical maps are standardly used to visualize anatomy and electrophysiological properties of the left atrium (LA) during pulmonary vein isolation (PVI) in atrial fibrillation (AF) patients. Purpose We sought to describe local differences in atrial conduction velocities (CVs), as a proof-of-principle, to study its association with tissue heterogeneity. We hypothesize that the variation and heterogeneity in these velocities throughout the LA carry important prognostic and diagnostic information, reflect the extent of remodeling and, in the future, might discern different subtypes of AF and treatment outcome. Methods We included AF patients who underwent PVI for the first time during 2021-2022. Electro-anatomical maps (EAMs) during sinus rhythm were acquired during the procedure and single data-points were projected on the patient-specific EAM-derived mesh of the LA. Patients were classified as persistent (AF lasting longer than 7 days and usually requiring electrical cardioversion) and paroxysmal (self-terminating AF episodes, lasting shorter than 7 days, mostly shorter than 24 hours) and were followed-up for 6 to 12-months. We determined unipolar voltages, activation times and computed local CVs for these patients. The CVs were normalized for each patients and reported as the median CV for each region containing enough points. Results We included 12 patients: 6 with paroxysmal and 6 with persistent AF. Patients in the paroxysmal group had larger median activation times and median CVs compared to the persistent group. The variability in voltage, activation time and CV was twice as large in the paroxysmal group (Table 1). Figure 1 displays an example of an electro-anatomical reconstruction of the LA of a paroxysmal AF patient showing the local median conduction velocity from an anterior and posterior view (Figure 1A and 1B) and the variance and distribution of median CV (Figure 1C). In this patient, we observed large local CV differences, which might reflect tissue heterogeneity (e.g. fibrosis). Conclusion We provided a proof-of-principle demonstrating that, with the use of conventional electro-anatomical maps, important information on heterogeneity and variance in local CVs can be quantified. We found a large variability in CV within and between patients. This can help discern different AF subtypes and might contribute to understanding different arrhythmogenic substrates and treatment outcome differences.

Comparison of combined substrate-based mapping techniques to identify critical sites for ventricular tachycardia ablation

Established electroanatomic mapping techniques for substrate mapping for ventricular tachycardia (VT) ablation includes voltage mapping, isochronal late activation mapping (ILAM), and fractionation mapping (FM). Omnipolar mapping (Abbott, Inc.) is a novel, optimized bipolar electrogram creation technique with integrated local conduction velocity annotation. The relative utilities of these mapping techniques are unknown. To evaluate the relative utility of various substrate mapping techniques for identification of critical sites for VT ablation. Electroanatomic substrate maps were created and retrospectively analyzed in 27 patients in whom 33 VT critical sites were identified. Both abnormal bipolar voltage and omnipolar voltage encompassed all critical sites and were observed over a median 66 (IQR: 41.3-86) cm2 and 52 (IQR 37.7-65.5) cm2, respectively. ILAM deceleration was observed over a median 9 (IQR 5.0, 11.1) cm2 and encompassed 22 (67%) critical sites, while abnormal omnipolar conduction velocity (OCV, <1mm/ms) was observed over 10 (IQR 5.3-16.6) cm2 and identified 22(67%) of critical sites, and fractionation mapping was observed over a median 4 (IQR 1.5, 7.6) cm2 and encompassed 20 (61%) critical sites. Mapping yield was greatest for Fractionation + OCV (2.1 critical sites / cm2), and least for bipolar voltage mapping (0.5 critical sites / cm2). OCV identified 100% of the critical sites in areas with a local point density >50 points/ cm2. ILAM, fractionation and omnipolar conduction velocity mapping each identified distinct critical sites and provided a smaller area of interest than voltage mapping alone. Sensitivity of novel mapping modalities improved with greater local point density.

Cell Unexcitability and Electrotonic Coupling Phenomenon Analysis of Ablation-Created Lesions: A Study Case with Ablated Explanted Human Heart.

This study investigates the effects of radiofrequency ablation (RFA)-created lesions on an explanted human heart in wedge preparation by simultaneous endo and sub-endo optical mapping. The heart in Langendorff perfusion was ablated under 40 W. The ventricle was stained with Vm sensitive dye Di-4-ANBDQPQ and two excitation light bands of different penetration depths were used (red = 660 nm, green = 525 nm) to perform a conduction velocity (CV) difference analysis for identification of CV alter-nans. The relative change in fluorescence (ΔF/F) traces were analyzed before and after ablation. Local activation time (LAT) was determined by the 50% approach. Local CV was obtained using the circle method, and RFA created lesions were characterized by examining the CV alternans correlated with transmural heterogeneities. The presence of CV alternans results from reduced excitability in a non-homogeneous lesion consisting of excitable and non-excitable cells. The absence of CV alternans in optical mapping with green light and their presence with deep-red light illustrates incomplete ablation across the ventricular wall or non-homogeneous ablation in the mid-myocardial layer. The presence of an intramural scar impairs the efficacy of the RFA procedure, suggesting a need for alternative ablations strategies.

Atrial fibrillatory wave amplitude revisited: A predictor of recurrence after catheter ablation independent of the degree of left atrial structural remodeling.

The fibrillatory wave amplitude (FWA) during atrial fibrillation (AF) is thought to reflect structural atrial remodeling, but it remains unclear what determines the FWA. 114 consecutive patients were prospectively studied who underwent catheter ablation of AF. The mean FWA was computed by automated surface ECG analyses. The extent of the left atrial (LA) voltage-defined atrial fibrosis and conduction properties were estimated by a three-dimensional high-density electroanatomical mapping system. The LA size was evaluated by transthoracic echocardiography. The study patients were divided into 2 groups according to an FWA in lead V1 above the median value of 46 µV (high FWA group, n=57) or below 46 µV (low FWA group, n=57). There were no differences in the age, gender, CHADS2 score, prevalence of paroxysmal AF, medications, ablation strategy, and LA volume index between the two groups. The LA low voltage areas in the low FWA group were not different from those in the high FWA group. The total LA activation time and local LA conduction velocity did not differ between the two groups. During a median follow-up of 710 days, the recurrence rate after ablation was significantly higher in patients with a low FWA than a high FWA (log-rank P=0.02). In a multivariate analysis, non-paroxysmal AF, the LA volume index, and FWA were independent predictors of recurrence after ablation. The FWA was not correlated with the markers of atrial structural remodeling. Nevertheless, the FWA could still provide information for predicting the clinical outcome after AF ablation.

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

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

Cardio PyMEA: A user-friendly, open-source Python application for cardiomyocyte microelectrode array analysis.

Open source analytical software for the analysis of electrophysiological cardiomyocyte data offers a variety of new functionalities to complement closed-source, proprietary tools. Here, we present the Cardio PyMEA application, a free, modifiable, and open source program for the analysis of microelectrode array (MEA) data obtained from cardiomyocyte cultures. Major software capabilities include: beat detection; pacemaker origin estimation; beat amplitude and interval; local activation time, upstroke velocity, and conduction velocity; analysis of cardiomyocyte property-distance relationships; and robust power law analysis of pacemaker spatiotemporal instability. Cardio PyMEA was written entirely in Python 3 to provide an accessible, integrated workflow that possesses a user-friendly graphical user interface (GUI) written in PyQt5 to allow for performant, cross-platform utilization. This application makes use of object-oriented programming (OOP) principles to facilitate the relatively straightforward incorporation of custom functionalities, e.g. power law analysis, that suit the needs of the user. Cardio PyMEA is available as an open source application under the terms of the GNU General Public License (GPL). The source code for Cardio PyMEA can be downloaded from Github at the following repository: https://github.com/csdunhamUC/cardio_pymea.

Endocardial and epicardial ECG imaging during sinus rhythm to detect local conduction delay in arrhythmogenic cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Dutch Heart Foundation Introduction We recently optimized our ECG imaging (ECGi) method for the estimation of endo- and epicardial activation during sinus rhythm. In patients with arrhythmogenic cardiomyopathy, late gadolinium enhancement (LGE)-CMR can identify regional myocardial injury and the combination of structural and electrical information may provide valuable insight in disease progression and risk stratification. However, the effect of structural disease and local conduction delay on the ECGi estimation of ventricular activation has not been studied. Purpose Evaluate the relation between LGE-CMR and non-invasively estimated local conduction velocity (CV). Methods 8 pathogenic mutation carriers (PKP2/PLN) underwent LGE-CMR for clinical follow up and 67 lead body surface mapping. Subject specific triangulated surface heart/torso/lung meshes were created. ECGi activation sequences were used to determine local CV with the triangulation method. The LGE location was identified according to the AHA 17 segment model. Per segment, variation in CV was computed and local activation timing maps and CV maps were constructed. Results Isochronal crowding was observed in subjects in segments with LGE (figure, red boxes) and locally, conduction velocity decreased. Variation in conduction velocity per segment in subjects with extensive LGE presence (&amp;gt;9 segments) was higher 0.031±0.018 vs. 0.026±0.013 m/s/cm2 in subjects without. Conclusion Our preliminary results indicate the ability of the ECGi method to identify regions with higher variation in local CV. This increase in CV variability might be used to assess the vulnerability to cardiac arrhythmia. Analysis will be extended towards the RV and subsequently, more subjects will be included.

PO-622-06 RELATIVE UTILITY OF OMNIPOLAR SUBSTRATE MAPPING FOR VENTRICULAR TACHYCARDIA ABLATION

EnSite Omnipolar mapping (Abbott, Abbott Park, IL, USA.) is a novel method of directionally optimized, high density, bipolar electrogram creation with integrated local conduction velocity annotation. Established electroanatomic mapping techniques for substrate mapping for ventricular tachycardia (VT) ablation includes voltage mapping, isochronal late activation mapping (ILAM), and fractionation mapping. The relative utilities of these mapping techniques is unknown.

Novel "late potential map" algorithm: Abnormal potentials and scar channels detection for ventricular tachycardia ablation.

Automated systems for substrate mapping in the context of ventricular tachycardia (VT) ablation may annotate far-field rather than near-field signals, rendering the resulting maps hard to interpret. Additionally, quantitative assessment of local conduction velocity (LCV) remains an unmet need in clinical practice. We evaluate whether a new late potential map (LPM) algorithm can provide an automatic and reliable annotation and localized bipolar voltage measurement of ventricular electrograms (EGMs) and if LCV analysis allows recognizing intrascar conduction corridors acting as VT isthmuses. In 16 patients referred for scar-related VT ablation, 8 VT activation maps and 29 high-resolution substrate maps from different activation wavefronts were obtained. In offline analysis, the LPM algorithm was compared to manually annotated substrate maps. Locations of the VT isthmuses were compared with the corresponding substrate maps in regard to LCV. The LPM algorithm had an overall/local abnormal ventricular activity (LAVA) annotation accuracy of 94.5%/81.1%, which compares to 83.7%/23.9% for the previous wavefront algorithm. The resultant maps presented a spatial concordance of 88.1% in delineating regions displaying LAVA. LAVA median localized bipolar voltage was 0.22 mV, but voltage amplitude assessment had modest accuracy in distinguishing LAVA from other abnormal EGMs (area under the curve: 0.676; p < .001). LCV analysis in high-density substrate maps identified a median of two intrascar conduction corridors per patient (interquartile range: 2-3), including the one acting as VT isthmus in all cases. The new LPM algorithm and LCV analysis may enhance substrate characterization in scar-related VT.

Atrial slow conduction develops and dynamically expands during premature stimulation in an animal model of persistent atrial fibrillation.

Slow conduction areas and conduction block in the atria are considered pro-arrhythmic conditions. Studies examining the size and distribution of slow conduction regions in the context of persistent atrial fibrillation (AF) may help to develop improved therapeutic strategies for patients with AF. In this work, we studied the differences of size and number in slow conduction areas between control and persistent AF goats and the influence of propagation direction on the development of these pathological conduction areas. Epicardial atrial electrical activations from the left atrial roof were optically mapped with physiological pacing cycle lengths and for the shortest captured cycle lengths. The recordings were converted to local activation times and conduction velocity measures. Regions with slow conduction velocity (less than ) were identified. The size of the connected regions and the number of non-connected regions were counted for propagation from different orthogonal directions. We found that regions of slow conduction significantly increases in our 15 persistent AF goat recordings in response to premature stimulation (24.4±4.3% increase to 36.6±4.4%, p < 0.001). This increase is driven by an increase of size from (3.70±0.89[mm2] to 6.36±0.91[mm2], p = 0.014) for already existing regions and not by generation of new slow conduction regions (11.6±1.8 vs. 13±1.9, p = 0.242). In 12 control goat recordings, no increase from baseline pacing to premature pacing was found. Similarly, size of the slow conduction areas and the count did not change significantly in control animals.

Reduction of Conduction Velocity in Patients with Atrial Fibrillation.

It is unknown to what extent atrial fibrillation (AF) episodes affect intra-atrial conduction velocity (CV) and whether regional differences in local CV heterogeneities exist during sinus rhythm. This case-control study aims to compare CV assessed throughout both atria between patients with and without AF. Patients (n = 34) underwent intra-operative epicardial mapping of the right atrium (RA), Bachmann’s bundle (BB), left atrium (LA) and pulmonary vein area (PVA). CV vectors were constructed to calculate median CV in addition to total activation times (TAT) and unipolar voltages. Biatrial median CV did not differ between patients with and without AF (90 ± 8 cm/s vs. 92 ± 6 cm/s, p = 0.56); only BB showed a CV reduction in the AF group (79 ± 12 cm/s vs. 88 ± 11 cm/s, p = 0.02). In patients without AF, there was no predilection site for the lowest CV (P5) (RA: 12%; BB: 29%; LA: 29%; PVA: 29%). In patients with AF, lowest CV was most often measured at BB (53%) and ranged between 15 to 22 cm/s (median: 20 cm/s). Lowest CVs were also measured at the LA (18%) and PVA (29%), but not at the RA. AF was associated with a prolonged TAT (p = 0.03) and decreased voltages (P5) at BB (p = 0.02). BB was a predilection site for slowing of conduction in patients with AF. Prolonged TAT and decreased voltages were also found at this site. The next step will be to determine the relevance of a reduced CV at BB in relation to AF development and maintenance.

CVAR-Seg: An Automated Signal Segmentation Pipeline for Conduction Velocity and Amplitude Restitution.

BackgroundRate-varying S1S2 stimulation protocols can be used for restitution studies to characterize atrial substrate, ionic remodeling, and atrial fibrillation risk. Clinical restitution studies with numerous patients create large amounts of these data. Thus, an automated pipeline to evaluate clinically acquired S1S2 stimulation protocol data necessitates consistent, robust, reproducible, and precise evaluation of local activation times, electrogram amplitude, and conduction velocity. Here, we present the CVAR-Seg pipeline, developed focusing on three challenges: (i) No previous knowledge of the stimulation parameters is available, thus, arbitrary protocols are supported. (ii) The pipeline remains robust under different noise conditions. (iii) The pipeline supports segmentation of atrial activities in close temporal proximity to the stimulation artifact, which is challenging due to larger amplitude and slope of the stimulus compared to the atrial activity.Methods and ResultsThe S1 basic cycle length was estimated by time interval detection. Stimulation time windows were segmented by detecting synchronous peaks in different channels surpassing an amplitude threshold and identifying time intervals between detected stimuli. Elimination of the stimulation artifact by a matched filter allowed detection of local activation times in temporal proximity. A non-linear signal energy operator was used to segment periods of atrial activity. Geodesic and Euclidean inter electrode distances allowed approximation of conduction velocity. The automatic segmentation performance of the CVAR-Seg pipeline was evaluated on 37 synthetic datasets with decreasing signal-to-noise ratios. Noise was modeled by reconstructing the frequency spectrum of clinical noise. The pipeline retained a median local activation time error below a single sample (1 ms) for signal-to-noise ratios as low as 0 dB representing a high clinical noise level. As a proof of concept, the pipeline was tested on a CARTO case of a paroxysmal atrial fibrillation patient and yielded plausible restitution curves for conduction speed and amplitude.ConclusionThe proposed openly available CVAR-Seg pipeline promises fast, fully automated, robust, and accurate evaluations of atrial signals even with low signal-to-noise ratios. This is achieved by solving the proximity problem of stimulation and atrial activity to enable standardized evaluation without introducing human bias for large data sets.

High-Resolution Measurement of Local Activation Time Differences From Bipolar Electrogram Amplitude

Localized changes in myocardial conduction velocity (CV) are pro-arrhythmic, but high-resolution mapping of local CV is not yet possible during clinical electrophysiology procedures. This is in part because measurement of local CV at small spatial scales (1 mm) requires accurate annotation of local activation time (LAT) differences with very high temporal resolution (≤1 ms), beyond that of standard clinical methods. We sought to develop a method for high-resolution measurement of LAT differences and validate against existing techniques. First, we use a simplified theoretical model to identify a quantitative relationship between the LAT difference of a pair of electrodes and the peak amplitude of the bipolar EGM measured between them. This allows LAT differences to be calculated from bipolar EGM peak amplitude, by a novel “Determination of EGM Latencies by Transformation of Amplitude” (DELTA) method. Next, we use simulated EGMs from a computational model to validate this method. With 1 kHz sampling, LAT differences less than 4 ms were more accurately measured with DELTA than by standard LAT annotation (mean error 3.8% vs. 22.9%). In a 1-dimensional and a 2-dimension model, CV calculations were more accurate using LAT differences found by the DELTA method than by standard LAT annotation (by unipolar dV/dt timing). DELTA-derived LAT differences were more accurate than standard LAT annotation in simulated complex fractionated EGMs from a model incorporating fibrosis. Finally, we validated the DELTA method in vivo using 18,740 bipolar EGMs recorded from the left atrium of 10 atrial fibrillation patients undergoing catheter ablation. Using clinical EGMs, there was agreement in LAT differences found by DELTA, standard LAT annotation, and unipolar waveform cross-correlation. These results demonstrate an underlying relationship between a bipolar EGM’s peak amplitude and the activation time difference between its two electrodes. Our computational modeling and clinical results suggest this relationship can be leveraged clinically to improve measurement accuracy for small LAT differences, which may improve CV measurement at small spatial scales.

Using machine learning to identify local cellular properties that support re-entrant activation in patient-specific models of atrial fibrillation.

AimsAtrial fibrillation (AF) is sustained by re-entrant activation patterns. Ablation strategies have been proposed that target regions of tissue that may support re-entrant activation patterns. We aimed to characterize the tissue properties associated with regions that tether re-entrant activation patterns in a validated virtual patient cohort.Methods and resultsAtrial fibrillation patient-specific models (seven paroxysmal and three persistent) were generated and validated against local activation time (LAT) measurements during an S1–S2 pacing protocol from the coronary sinus and high right atrium, respectively. Atrial models were stimulated with burst pacing from three locations in the proximity of each pulmonary vein to initiate re-entrant activation patterns. Five atria exhibited sustained activation patterns for at least 80 s. Models with short maximum action potential durations (APDs) were associated with sustained activation. Phase singularities were mapped across the atria sustained activation patterns. Regions with a low maximum conduction velocity (CV) were associated with tethering of phase singularities. A support vector machine (SVM) was trained on maximum local conduction velocity and action potential duration to identify regions that tether phase singularities. The SVM identified regions of tissue that could support tethering with 91% accuracy. This accuracy increased to 95% when the SVM was also trained on surface area.ConclusionIn a virtual patient cohort, local tissue properties, that can be measured (CV) or estimated (APD; using effective refractory period as a surrogate) clinically, identified regions of tissue that tether phase singularities. Combing CV and APD with atrial surface area further improved the accuracy in identifying regions that tether phase singularities.

Accuracy of left atrial fibrosis detection with cardiac magnetic resonance: correlation of late gadolinium enhancement with endocardial voltage and conduction velocity.

Myocardial fibrosis is a hallmark of atrial fibrillation (AF) and its characterization could be used to guide ablation procedures. Late gadolinium enhanced-magnetic resonance imaging (LGE-MRI) detects areas of atrial fibrosis. However, its accuracy remains controversial. We aimed to analyse the accuracy of LGE-MRI to identify left atrial (LA) arrhythmogenic substrate by analysing voltage and conduction velocity at the areas of LGE. Late gadolinium enhanced-magnetic resonance imaging was performed before ablation in 16 patients. Atrial wall intensity was normalized to blood pool and classified as healthy, interstitial fibrosis, and dense scar tissue depending of the resulting image intensity ratio. Bipolar voltage and local conduction velocity were measured in LA with high-density electroanatomic maps recorded in sinus rhythm and subsequently projected into the LGE-MRI. A semi-automatic, point-by-point correlation was made between LGE-MRI and electroanatomical mapping. Mean bipolar voltage and local velocity progressively decreased from healthy to interstitial fibrosis to scar. There was a significant negative correlation between LGE with voltage (r = -0.39, P < 0.001) and conduction velocity (r = -0.25, P < 0.001). In patients showing dilated atria (LA diameter ≥45 mm) the conduction velocity predictive capacity of LGE-MRI was weaker (r = -0.40 ± 0.09 vs. -0.20 ± 0.13, P = 0.02). Areas with higher LGE show lower voltage and slower conduction in sinus rhythm. The enhancement intensity correlates with bipolar voltage and conduction velocity in a point-by-point analysis. The performance of LGE-MRI in assessing local velocity might be reduced in patients with dilated atria (LA diameter ≥45).

Abstract 15418: An Arrhythmogenic Isolated Septal Aneurysm

Background: Septal infarct due to isolated occlusion of a perforator branch is extremely rare. Few reported cases only describe either the EKG findings, imaging abnormalities or revascularization techniques. Objective: We report a case of an isolated septal aneurysm (ISA) caused by the acute occlusion of the second septal perforator presenting with recurrent ventricular fibrillation (VF). Results: A 63 year old woman presented to the hospital with chest pain. EKG showed an ST segment elevation localized to lead V3 (Fig1A), troponin 18.23. Angiogram showed an isolated 95% tubular stenosis of large second septal branch of LAD (Fig1B). No revascularization was performed. The patient subsequently had cardiac arrest (VF) requiring cardioversion. Repeat angiogram was unchanged. Echo showed isolated mid septal dyskinetic segment (Fig1C). LVEF was 60%. The patient was discharged with an external defibrillator. Repeat echo showed unchanged EF but presence of the isolated dyskinetic segment. An electrophysiologic study (EPS) showed VF induced with 2 extra stimuli at 250 ms with a drive cycle of 600 ms (Fig1D). An ICD was implanted for prevention of SCD. Conclusion: We describe the first case of an arrhythmogenic ISA in the presence of normal LVEF. The interventricular septum is composed of right and left ventricular endocardium. Experiments have shown that acute septal ischemia produces trans-septal asymmetry in expression of membrane ion channels and action potentials in local conduction velocity and gradients. This results in trans-mural heterogeneity of tissue excitability, a substrate for transmural re-entry and ventricular tachyarrhythmias, in septal infarction. This also explains the persistence of enhanced arrhythmogenicity in our patient during the initial and chronic phases of ischemia. ISA is rare but potentially arrhythmogenic. ISA with preserved LVEF, EPS for arrhythmogenicity and ICD for secondary prevention of SCD should be considered in such cases.