Spatial reproducibility of complex fractionated atrial electrogram depending on the direction and configuration of bipolar electrodes: an in-silico modeling study.

Although 3D-complex fractionated atrial electrogram (CFAE) mapping is useful in radiofrequency catheter ablation for persistent atrial fibrillation (AF), the directions and configuration of the bipolar electrodes may affect the electrogram. This study aimed to compare the spatial reproducibility of CFAE by changing the catheter orientations and electrode distance in an in-silico left atrium (LA). We conducted this study by importing the heart CT image of a patient with AF into a 3D-homogeneous human LA model. Electrogram morphology, CFAE-cycle lengths (CLs) were compared for 16 different orientations of a virtual bipolar conventional catheter (conv-cath: size 3.5 mm, inter-electrode distance 4.75 mm). Additionally, the spatial correlations of CFAE-CLs and the percentage of consistent sites with CFAE-CL<120 ms were analyzed. The results from the conv-cath were compared with that obtained using a mini catheter (mini-cath: size 1 mm, inter-electrode distance 2.5 mm). Depending on the catheter orientation, the electrogram morphology and CFAE-CLs varied (conv-cath: 11.5±0.7% variation, mini-cath: 7.1±1.2% variation), however the mini-cath produced less variation of CFAE-CL than conv-cath (p<0.001). There were moderate spatial correlations among CFAE-CL measured at 16 orientations (conv-cath: r=0.3055±0.2194 vs. mini-cath: 0.6074±0.0733, p<0.001). Additionally, the ratio of consistent CFAE sites was higher for mini catheter than conventional one (38.3±4.6% vs. 22.3±1.4%, p<0.05). Electrograms and CFAE distribution are affected by catheter orientation and electrode configuration in the in-silico LA model. However, there was moderate spatial consistency of CFAE areas, and narrowly spaced bipolar catheters were less influenced by catheter direction than conventional catheters.

Sensitivity and specificity of substrate mapping: an in silico framework for the evaluation of electroanatomical substrate mapping strategies.

BACKGROUND: Voltage mapping is an important tool for characterizing proarrhythmic electrophysiological substrate, yet it is subject to geometric factors that influence bipolar amplitudes and thus compromise performance. The aim of this study was to characterize the impact of catheter orientation on the ability of bipolar amplitudes to accurately discriminate between healthy and diseased tissues. METHODS AND RESULTS: We constructed a 3-dimensional, in silico, bidomain model of cardiac tissue containing transmural lesions of varying diameter. A planar excitation wave was stimulated and electrograms were sampled with a realistic catheter model at multiple positions and orientations. We carried out validation studies in animal experiments of acute ablation lesions mapped with a clinical mapping system. Bipolar electrograms sampled at higher inclination angles of the catheter with respect to the tissue demonstrated improvements in both sensitivity and specificity of lesion detection. Removing low-voltage electrograms with concurrent activation of both electrodes, suggesting false attenuation of the bipolar electrogram due to alignment with the excitation wavefront, had little effect on the accuracy of voltage mapping. CONCLUSIONS: Our results demonstrate possible mechanisms for the impact of catheter orientation on voltage mapping accuracy. Moreover, results from our simulations suggest that mapping accuracy may be improved by selectively controlling the inclination of the catheter to record at higher angles with respect to the tissue.

Successful treatment of macroreentrant atrial tachycardia by radiofrequency ablation targeting channels with continuous activation.

BACKGROUND: Macroreentrant atrial tachycardia (MRAT) is frequently unresponsive to antiarrhythmic drugs. The application of three-dimensional (3D) mapping and entrainment pacing contributes to a high success rate for radiofrequency ablation, but programmed electrical pacing may either terminate or transform clinical tachyarrhythmias. On the basis of clinical experiences of the use of ventricular tachycardia ablation, channels with continuous activation are suitable for reentrant circuits, and ablation at these channels can lead to noninducibility of ventricular tachycardias. We reviewed patients referred for symptomatic MRAT with identified channels with continuous activation and evaluated the efficacy of MRAT ablation by targeting these channels. METHODS: Fifteen consecutive patients (10 men, 49 ± 14 years) with MRAT illustrated by endocardial activation maps using a 3D electroanatomical mapping system (CARTO™, Biosense Webster, Diamond Bar, CA, USA) were included in this study. Continuous activation was defined as double or continuous potentials without an isoelectric interval, and sites with continuous activation were tagged for measurements of channel properties. Radiofrequency ablation was performed at those targeted sites located within the reentrant circuit. RESULTS: Radiofrequency ablation successfully eliminated MRAT in all patients. The mean cycle length was 283 ± 60 ms, and the longest activation duration was 112 ± 38 ms. The minimal and maximal bipolar voltage amplitudes were 0.13 ± 0.1 mV and 0.7 ± 0.6 mV, respectively. The targeted ablation length and width were 28.9 ± 15.3 mm and 9.4 ± 3.3 mm, respectively. CONCLUSION: Radiofrequency ablation of MRAT targeting channels with continuous activation using a 3D electroanatomical mapping system yields a high success rate.

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

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

Initial negative concordance on unipolar and bipolar electrograms: a novel parameter for localizing the origin of premature ventricular contractions arising from pulmonary sinus cusps.

BACKGROUND: The features of the unipolar electrogram (UEGM) and bipolar electrogram (BEGM) have been utilized to identify the site of origin of idiopathic premature ventricular contractions (PVCs) arising from pulmonary sinus cusps (PSCs), but for these PVCs, whether a negative concordance in the initial waves of both EGMs recorded above pulmonary valves can be used as a parameter to localize the origin has not been previously studied. We aimed to assess whether an initial negative concordance (INC) between the UEGM and BEGM might determine the origin of PVCs mapped and ablated within PSCs. METHODS: Data were collected from 22 patients undergoing successful radiofrequency catheter ablation for symptomatic idiopathic PVCs within PSCs. The morphological features of both the UEGM and the BEGM recorded at all ablation sites were analyzed. RESULTS: A total of 109 sites within PSCs were ablated in 22 patients with an age (mean ± SD) of 47.2 ± 17.2 years. Ablation resulted in procedural success in all patients. The INC was observed at 18 of 22 (81.8%) successful ablation sites, contrasted with 3 of 87 (3.4%) unsuccessful sites (P < 0.001). The INC was consistent with the outcomes of conventional mapping parameters and proved to be an additional useful predictor of ablation success, with a sensitivity, specificity, positive predictive value and negative predictive value of 81.8%, 96.6%, 85.7% and 95.5%, respectively. CONCLUSIONS: An INC between the UEGM and the BEGM can predict the origin of PVCs arising from PSCs. An initial negative concordance between unipolar and bipolar electrograms indicates that the distal electrode of the ablation catheter is at the origin of premature ventricular contractions within pulmonary sinus cusps.

Utility and limitations of coherent mapping algorithm utilizing vectors and global propagation patterns in atrial tachycardia.

Background: A novel mapping algorithm utilizing vectors and global patterns of propagation (Coherent™, Biosense Webster) has been developed to help identify the mechanism of atrial tachycardia (AT). We aimed to determine the diagnostic accuracy of coherent mapping compared with that of ripple mapping. Methods and results: This study included 41 consecutive patients with 84 ATs (47 reentrant and 37 focal ATs). Two independent electrophysiologists confirmed the diagnoses using coherent mapping before the ripple map-guided ablation. AT termination was achieved in 75 of 84 ATs (89%) at first ablation lesion set. Four of the remaining nine ATs, which were terminated before an index radiofrequency (RF) application, were non-inducible after RF delivery at the first lesion set, whereas the other five ATs were terminated at the second lesion set. Diagnostic agreement between coherent and ripple maps was achieved in 51 of 84 ATs (61%): 28 of the 47 macroreentrant ATs (60%) and 23 of the 37 focal ATs (62%; P = 0.826). In typical macroreentrant ATs, including left atrial roof, perimitral, and cavotricuspid isthmus-dependent ATs, coherent maps achieved diagnostic agreement in 23 of 29 ATs (79%), which was higher than that in other ATs (51%, P = 0.018): 13 of 26 macroreentrant ATs (50%) and 15 of 29 focal ATs (52%, P = 1.000). Conclusion: Ripple map-guided AT ablation achieved a high termination rate in the first lesion set. Coherent mapping yielded a favorable diagnostic accuracy for typical macroreentrant ATs, though its value for diagnosing other ATs was limited.

Limitations of Unipolar Signals in Guiding Successful Outflow Tract Premature Ventricular Contraction Ablation.

BACKGROUND: Unipolar electrograms (UniEGMs) are commonly used to annotate earliest local activation of focal arrhythmias. However, their utility in guiding premature ventricular contractions (PVCs) ablation may be limited when the PVC source is less superficial. OBJECTIVES: The authors sought to compare bipolar electrograms (BiEGMs) vs UniEGMs in guiding successful ablation of right ventricular outflow tract (RVOT) vs intramural outflow tract (OT) PVCs. The authors hypothesized that: 1) earliest bipolar local activation time (LATBi) would better guide mapping and ablation, vs UniEGM dV/dt (LATUni) or QS morphology; and 2) LAT differences using bipolar vs unipolar EGMs (ΔLATBi-Uni) would be greater for intramural OT than RVOT PVCs. METHODS: Consecutive patients undergoing successful PVC ablation 2017 to2020 requiring only RVOT or RVOT+left ventricular OT (RVOT+LVOT) ablation were retrospectively analyzed. BiEGMs and UniEGMs at successful ablation sites were compared. RESULTS: Of 70 patients, 50 required RVOT-only, and 20 required RVOT+LVOT ablation for acute and long-term PVC suppression. Mean ΔLATBi-Uni was lower for RVOT vs RVOT+LVOT groups (9.3 ± 6.4 ms vs 17.4 ± 9.9 ms; P < 0.01). QS UniEGM was seen in 78% of RVOT, compared with 53% of RVOT+LVOT patients (P < 0.016). RVOT+LVOT sites most frequently included the posteroseptal RVOT and adjacent LVOT (73%), and 43% lacked a QS unipolar EGM. ΔLATBi-Uni ≥15 ms best distinguished sites in which RVOT-only vs RVOT+LVOT ablation achieved acute PVC suppression (area under the curve: 0.77). CONCLUSIONS: Earliest BiEGM activation guides successful ablation of OT PVCs better than UniEGM-guided analysis, especially when an intramural PVC source is present.

Idiopathic Ventricular Arrhythmias Ablated in Different Subregions of the Aortic Sinuses of Valsalva: Anatomical Distribution, Precordial Electrocardiographic Notch Patterns, and Bipolar Electrographic Characteristics.

Background: Little is known about the differences among ventricular arrhythmias (VAs) ablated in different subregions of the aortic sinuses of Valsalva (ASVs). We aim to investigate the distribution, precordial electrocardiographic patterns, and bipolar electrogram characteristics of VAs ablated in different subregions of the ASVs. Methods: We divided the right ASV and the left ASV into a total of 6 subregions and studied 51 idiopathic VAs ablated first time successfully in the ASVs. Results: These 51 VAs were inhomogeneously distributed among the 6 subregions, which comprised the right-lateral ASV (1/51), the right-anterior ASV (11/51), the regions along the right (13/51) and left (9/51) sides of the ASV junction, the left-anterior ASV (5/51), and the left-lateral ASV (12/51). Fractionated potentials were dominant (39/51, 76%) among the 3 types of target electrograms. From the right-lateral ASV to the left-lateral ASV, the percentage of fractionated potentials gradually decreased from 100 to 59%. A precordial rebound notch in V3-V4 or V4-V5 had sensitivity of 90.9%, specificity of 85.0%, and negative predictive value (NPV) of 97.1% to predict VAs ablated in the right-anterior ASV. A precordial rebound notch in V2-V3 had sensitivity of 50.0%, specificity of 94.9%, and NPV of 86.0% to predict VAs ablated in the left-lateral ASV. Conclusion: VA targets were mainly distributed in the anterior and the left-lateral ASVs. Fractionated potentials were common among target electrograms, especially in theright-anterolateral ASV. Precordial electrocardiographic rebound notch has high predictive accuracy in identifying different subregions of the ASVs as target ablation sites.

Mechanism and magnitude of bipolar electrogram directional sensitivity: Characterizing underlying determinants of bipolar amplitude.

BACKGROUND: The amplitude of bipolar electrograms (EGMs) is directionally sensitive, decreasing when measured from electrode pairs oriented oblique to a propagating wavefront. OBJECTIVE: The purpose of this study was to use a computational model and clinical data to establish the mechanism and magnitude of directional sensitivity. METHODS: Simulated EGMs were created using a computational model with electrode pairs rotated relative to a passing wavefront. A clinical database of 18,740 EGMs with varying electrode separation and orientations was recorded from the left atrium of 10 patients with atrial fibrillation during pacing. For each EGM, the angle of incidence between the electrodes and the wavefront was measured using local conduction velocity (CV) mapping. RESULTS: A theoretical model was derived describing the effect of the changing angle of incidence, electrode spacing, and CV on the local activation time difference between a pair of electrodes. Model predictions were validated using simulated and clinical EGMs. Bipolar amplitude measured by an electrode pair is decreased (directionally sensitive) at angles of incidence resulting in local activation time differences shorter than unipolar downstroke duration. Directional sensitivity increases with closer electrode spacing, faster CV, and longer unipolar EGM duration. For narrowly spaced electrode pairs (<5 mm), it is predicted at all orientations. CONCLUSION: Directional sensitivity occurs because bipolar amplitude is reduced when the component unipolar EGMs overlap, such that neither electrode is "indifferent." At the electrode spacing of clinical catheters, this is predicted to occur regardless of catheter orientation. This suggests that bipolar directional sensitivity can be lessened but not overcome by recently introduced catheters with additional rotated electrode pairs.

The Amplitude-Normalized Area of a Bipolar Electrogram as a Measure of Local Conduction Delay in the Heart.

BACKGROUND: Re-entrant ventricular tachycardia may be non-inducible or haemodynamically compromising, requiring assessment of the electrophysiological properties of the myocardium during sinus rhythm (i.e., substrate mapping). Areas of heart tissue with slow conduction can act as a critical isthmus for re-entrant electrical excitation and are a potential target for ablation therapy. AIM: To develop and validate a novel metric of local conduction delay in the heart, the amplitude-normalized electrogram area (norm_EA). METHODS: A computational model of a propagating mouse action potential was used to establish the impact of altering sodium channel conductance, intracellular conductivity, fibrosis density, and electrode size/orientation on bipolar electrogram morphology. Findings were then validated in experimental studies in mouse and guinea pig hearts instrumented for the recording of bipolar electrograms from a multipolar linear mapping catheter. norm_EA was calculated by integrating the absolute area of a bipolar electrogram divided by the electrogram amplitude. Electrogram metrics were correlated with the local conduction delay during sodium channel block, gap junction inhibition, and acute ischemia. RESULTS: In computational simulations, reducing sodium channel conductance and intracellular conductivity resulted in a decrease in signal amplitude and increase in norm_EA (reflecting a broadening of electrogram morphology). For larger electrodes (3 mm diameter/7.1 mm2 area), the change in norm_EA was essentially linear with the change in local conduction delay. Experimental studies supported this finding, showing that the magnitude of change in norm_EA induced by flecainide (1-4 µM), carbenoxolone (10-50 µM), and low-flow ischemia (25% of initial flow rate) was linearly correlated with the local conduction delay in each condition (r 2 = 0.92). Qualitatively similar effects were observed in guinea pig hearts perfused with flecainide. Increasing fibrosis density in the computational model also resulted in a decrease in signal amplitude and increase in norm_EA. However, this remains to be validated using experimental/clinical data of chronic infarct. CONCLUSION: norm_EA is a quantitative measure of local conduction delay between the electrode pair that generates a bipolar electrogram, which may have utility in electrophysiological substrate mapping of non-inducible or haemodynamically compromising tachyarrhythmia.

Determinants of atrial bipolar voltage: Inter electrode distance and wavefront angle.

BACKGROUND: Local bipolar electrogram (EGM) peak-to-peak voltage (Vpp) is currently used to characterise mapped myocardial substrate. However, how interelectrode distance and angle of wavefront incidence affect bipolar, Vpp values, in the current era of multi-electrode mapping is unknown. OBJECTIVES: To elucidate the effects of tissue and electrode geometry on bipolar Vpp measurements, when mapping healthy versus diseased atrial regions. METHODS: A bidomain model of human atrial tissue was used to quantify the influence on Vpp values of various electrode configurations in healthy tissue, and tissue containing an unexcitable region. The orientation angle and interelectrode spacing of a surface bipole, and thickness and depth of the unexcitable core were serially varied. Results were validated with data obtained from isolated porcine hearts. RESULTS: In healthy tissue, bipolar Vpp values increased with increasing interelectrode spacing and plateaued beyond a spacing of approximately 4 mm. The bipolar Vpp values in healthy tissue were relatively less sensitive to wavefront orientation angle with large interelectrode spacing. In diseased tissue, on the contrary, with increasing interelectrode spacing, bipolar Vpp values increased linearly without a plateau and were more sensitive to orientation angle. The bipolar Vpp values decreased with increasing thickness of the scar, with larger relative decrease in small bipoles than larger ones. Bipolar Vpp values increased with a progressively intramural location of fixed-size scar and became less distinguishable from healthy tissue especially for smaller interelectrode spacings. CONCLUSIONS: The scalable relationship established for interelectrode distances favour an electric-field-based assessment as opposed to traditional Vpp values as a tool for physiologically relevant measurement for mapping catheters with interelectrode spacing up to 4 mm. This will allow for universal assessment of myocardial health across catheters with varied spacing.