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Unipolar electrogram‐based voltage mapping with far‐field cancellation to improve detection of abnormal atrial substrate during atrial fibrillation
Abstract
Introduction
An important substrate for AF is fibrotic atrial myopathy. Identifying low‐voltage, myopathic regions during AF using traditional bipolar voltage mapping is limited by the directional‐dependency of wave propagation. Our objective was to evaluate directionally‐independent unipolar voltage mapping, but with far‐field cancellation, to identify low‐voltage regions during AF.
Methods
In 12 patients undergoing pulmonary vein isolation for AF, high‐resolution voltage mapping was performed in the left atrium during sinus rhythm and AF using a roving 20‐pole circular catheter. Bipolar EGMs (Bi) <0.5mV in sinus rhythm identified low‐voltage regions. During AF, bipolar voltage and unipolar voltage maps were created, the latter with (uni‐res) and without (uni‐orig) far‐field cancellation using a novel, validated least‐squares algorithm.
Results
Uni‐res voltage was ~25% lower than uni‐orig for both low‐voltage and normal atrial regions. Far‐field EGM had a dominant frequency (DF) of 4.5‐6.0Hz, and its removal resulted in a lower DF for uni‐orig compared to uni‐res (5.1±1.5Hz vs. 4.8±1.5Hz, p<0.001). Compared to Bi, uni‐res had significantly greater area under the receiver operator curve (0.80 vs. 0.77, p<0.05), specificity (86% vs. 76%, p<0.001) and positive predictive value (43% vs. 30%, p<0.001) for detecting low‐voltage during AF. Similar improvements in specificity and positive predictive value were evident for uni‐res vs. uni‐orig.
Conclusion
Far‐field EGM can be reliably removed from uni‐orig using our novel, least squares algorithm. Compared to Bi and uni‐orig, uni‐res is more accurate in detecting low‐voltage regions during AF. This approach may improve substrate mapping and ablation during AF, and merits further study.
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... BEs are obtained through the subtraction of two adjacent UEs [7]. BEs eliminate far-field electrical activation, but are more challenging to interpret as their signal depends on the relative orientation of the inter-electrode axis to the incident electrical wavefront [8]. A recently developed technique combines multiple unipolar electrograms to compute an omnipolar electrogram (OE), which overcomes these limitations. ...
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.
Background:
Bipolar electrogram voltage during sinus rhythm (VSR) has been used as a surrogate for atrial fibrosis in guiding catheter ablation of persistent atrial fibrillation (AF), but the fixed rate and wavefront characteristics present during sinus rhythm may not accurately reflect underlying functional vulnerabilities responsible for AF maintenance.
Objective:
The purpose of this study was determine whether, given adequate temporal sampling, the spatial distribution of mean AF voltage (VmAF) better correlates with delayed-enhancement magnetic resonance imaging (MRI-DE)-detected atrial fibrosis than VSR.
Methods:
AF was mapped (8 seconds) during index ablation for persistent AF (20 patients) using a 20-pole catheter (660 ± 28 points/map). After cardioversion, VSR was mapped (557 ± 326 points/map). Electroanatomic and MRI-DE maps were co-registered in 14 patients.
Results:
The time course of VmAF was assessed from 1-40 AF cycles (∼8 seconds) at 1113 locations. VmAF stabilized with sampling >4 seconds (mean voltage error 0.05 mV). Paired point analysis of VmAF from segments acquired 30 seconds apart (3667 sites; 15 patients) showed strong correlation (r = 0.95; P <.001). Delayed enhancement (DE) was assessed across the posterior left atrial (LA) wall, occupying 33% ± 13%. VmAF distributions were (median [IQR]) 0.21 [0.14-0.35] mV in DE vs 0.52 [0.34-0.77] mV in non-DE regions. VSR distributions were 1.34 [0.65-2.48] mV in DE vs 2.37 [1.27-3.97] mV in non-DE. VmAF threshold of 0.35 mV yielded sensitivity of 75% and specificity of 79% in detecting MRI-DE compared with 63% and 67%, respectively, for VSR (1.8-mV threshold). CONCLUSION: The correlation between low-voltage and posterior LA MRI-DE is significantly improved when acquired during AF vs sinus rhythm. With adequate sampling, mean AF voltage is a reproducible marker reflecting the functional response to the underlying persistent AF substrate.
Background:
Direct impact of bipolar orientation on electrograms remains unknown.
Objective:
To examine the variation of electrograms with diagonally orthogonal bipoles.
Methods:
The HD-32 GridTM-catheter can assess the impact of bipolar orientation while keeping inter-electrode distance and center unchanged. Seven sheep with anterior myocardial infarction were analyzed with diagonally orthogonal electrode pairs across splines, comparing local EGMs from each pair of opposing electrodes (ex. A1-B3 [south-east direction (SE)] vs. A3-B1 [north-east direction (NE)]).
Results:
4084 EGMs (one in each direction) were analyzed for 2042 sites (544 infarcted area, 488 border area, and 1010 normal area). The higher- and lower-voltages measured by each pair of opposing electrodes significantly differed (1.10mV[0.43mV-2.56mV] vs. 0.69mV[0.28mV-1.58mV], P<0.0001), and the median variation was 0.28mV[0.11mV-0.80mV] (31.7%[16.0%-48.9%]). The voltage variation was maximized to 48.7%[37.7-61.6%] (P<0.0001) on sites where the activation front was perpendicular to the one bipolar direction and parallel to the other. 594/719 (82.6%) sites with the voltage<0.5mV and 539/699 (77.1%) sites with the voltage>1.5mV in NE stayed in the same voltage range in SE. However, only 348/624 (55.8%) sites with the voltage 0.5-1.5 mV in the NE stayed in the same range in SE. LAVAs were detected in 592/2042 (29.0%) in total, frequently distributed in the border area. 177 (29.9%) of LAVAs were missed with one direction and 180 (30.4%) in the other. When the LAVAs detected by NE (n=415) are defined as the reference, 235/415 (56.6%) matched with the SE.
Conclusion:
The bipolar voltage and distribution of LAVAs may significantly differ between diagonally orthogonal bipolar pairs at any given site.
Background:
Validation of voltage-based scar delineation has been limited to small populations using mainly endocardial measurements. The aim of this study is to compare unipolar voltage amplitudes (UnipV) with scar on delayed enhancement cardiac magnetic resonance imaging (DE-CMR).
Methods:
Heart failure patients who underwent DE-CMR and electro-anatomic mapping were included. Thirty-three endocardial mapped patients and 27 epicardial mapped patients were investigated. UnipV were computed peak-to-peak. Electrograms were matched with scar extent of the corresponding DE-CMR segment using a 16-segment/slice model. Non-scar was defined as 0% scar, while scar was defined as 1-100% scar extent.
Results:
UnipVs were moderately lower in scar than in non-scar (endocardial 7.1 [4.6-10.6] vs. 10.3 [7.4-14.2] mV; epicardial 6.7 [3.6-10.5] vs. 7.8 [4.2-12.3] mV; both p<0.001). The correlation between UnipV and scar extent was moderate for endocardial (R = -0.33, p<0.001), and poor for epicardial measurements (R = -0.07, p<0.001). Endocardial UnipV predicted segments with >25%, >50% and >75% scar extent with AUCs of 0.72, 0.73 and 0.76, respectively, while epicardial UnipV were poor scar predictors, independent of scar burden (AUC = 0.47-0.56). UnipV in non-scar varied widely between patients (p<0.001) and were lower in scar compared to non-scar in only 9/22 (41%) endocardial mapped patients and 4/19 (21%) epicardial mapped patients with scar.
Conclusion:
UnipV are slightly lower in scar compared to non-scar. However, significant UnipV differences between and within patients and large overlap between non-scar and scar limits the reliability of accurate scar assessment, especially in epicardial measurements and in segments with less than 75% scar extent.
Background—
The presence of focal fibrillation waves during atrial fibrillation (AF) can, besides ectopic activity, also be explained by asynchronous activation of the atrial endo- and epicardial layer and transmurally propagating fibrillation waves. To provide direct proof of endo-epicardial asynchrony, we performed simultaneous high-resolution mapping of the right atrial endo- and epicardial wall during AF in humans.
Method and Results—
Intraoperative mapping of the endo- and epicardial right atrial wall was performed during (induced) AF in 10 patients with AF (paroxysmal: n=3; persistent: n=4; and longstanding persistent: n=3) and 4 patients without a history of AF. A clamp made of 2 rectangular 8×16 electrode arrays (interelectrode distance 2 mm) was inserted into the incision in the right atrial appendage. Recordings of 10 seconds of AF were analyzed to determine the incidence of asynchronous endo-epicardial activation times (≥15 ms) of opposite electrodes. Asynchronous endo-epicardial activation ranged between 0.9 and 55.9% without preference for either side. Focal waves appeared equally frequent at endocardium and epicardium (11% versus 13%; P =0.18). Using strict criteria for breakthrough (presence of an opposite wave within 4 mm and ≤14 ms before the origin of the focal wave), the majority (65%) of all focal fibrillation waves could be attributed to endo-epicardial excitation.
Conclusions—
We provided the first evidence for asynchronous activation of the endo-epicardial wall during AF in humans. Endo-epicardial asynchrony may play a major role in the pathophysiology of AF and may offer an explanation why in some patients therapy fails.
Aims:
The mechanisms underlying persistent atrial fibrillation (AF) in patients with atrial fibrosis are poorly understood. The goal of this study was to use patient-derived atrial models to test the hypothesis that AF reentrant drivers (RDs) persist only in regions with specific fibrosis patterns.
Methods and results:
20 patients with persistent AF (PsAF) underwent late gadolinium-enhanced MRI to detect presence of atrial fibrosis. Segmented images were used to construct personalised 3D models of the fibrotic atria with biophysically realistic atrial electrophysiology. In each model, rapid pacing was applied to induce AF. AF dynamics were analysed and RDs were identified using phase mapping. Fibrosis patterns in RD regions were characterised by computing maps of fibrosis density (FD) and entropy (FE). AF was inducible in 13/20 models and perpetuated by few RDs (2.7±1.5) that were spatially confined (trajectory of phase singularities: 7.6±2.3mm). Compared to the remaining atrial tissue, regions where RDs persisted had higher FE (IQR: 0.42-0.60 vs 0.00-0.40, p<0.05) and FD (IQR: 0.59-0.77 vs 0.00-0.33, p<0.05). Machine learning classified RD and non-RD regions based on FD and FE and identified a subset of fibrotic boundary zones present in 13.8±4.9% of atrial tissue where 83.5±2.4% of all RD phase singularities were located.
Conclusions:
Patient-derived models demonstrate that AF in fibrotic substrates is perpetuated by RDs persisting in fibrosis boundary zones characterised by specific regional fibrosis metrics (high FE and FD). These results provide new insights into the mechanisms that sustain PsAF and could pave the way for personalised, MRI-based management of PsAF.
In the past decade, catheter ablation has become an established therapy for symptomatic atrial fibrillation (AF). Until very recently, few data have been available to guide the clinical community on the outcomes of AF ablation at ≥3 years of follow-up. We aimed to systematically review the medical literature to evaluate the long-term outcomes of AF ablation.
A structured electronic database search (PubMed, Embase, Web of Science, Cochrane) of the scientific literature was performed for studies describing outcomes at ≥3 years after AF ablation, with a mean follow-up of ≥24 months after the index procedure. The following data were extracted: (1) single-procedure success, (2) multiple-procedure success, and (3) requirement for repeat procedures. Data were extracted from 19 studies, including 6167 patients undergoing AF ablation. Single-procedure freedom from atrial arrhythmia at long-term follow-up was 53.1% (95% CI 46.2% to 60.0%) overall, 54.1% (95% CI 44.4% to 63.4%) in paroxysmal AF, and 41.8% (95% CI 25.2% to 60.5%) in nonparoxysmal AF. Substantial heterogeneity (I(2)>50%) was noted for single-procedure outcomes. With multiple procedures, the long-term success rate was 79.8% (95% CI 75.0% to 83.8%) overall, with significant heterogeneity (I(2)>50%).The average number of procedures per patient was 1.51 (95% CI 1.36 to 1.67).
Catheter ablation is an effective and durable long-term therapeutic strategy for some AF patients. Although significant heterogeneity is seen with single procedures, long-term freedom from atrial arrhythmia can be achieved in some patients, but multiple procedures may be required.
This contribution addresses the extraction of atrial activity (AA) from real electrocardiogram (ECG) recordings of atrial fibrillation (AF). We show the appropriateness of independent component analysis (ICA) to tackle this biomedical challenge when regarded as a blind source separation (BSS) problem. ICA is a statistical tool able to reconstruct the unobservable independent sources of bioelectric activity which generate, through instantaneous linear mixing, a measurable set of signals. The three key hypothesis that make ICA applicable in the present scenario are discussed and validated: 1) AA and ventricular activity (VA) are generated by sources of independent bioelectric activity; 2) AA and VA present non-Gaussian distributions; and 3) the generation of the surface ECG potentials from the cardioelectric sources can be regarded as a narrow-band linear propagation process. To empirically endorse these claims, an ICA algorithm is applied to recordings from seven patients with persistent AF. We demonstrate that the AA source can be identified using a kurtosis-based reordering of the separated signals followed by spectral analysis of the sub-Gaussian sources. In contrast to traditional methods, the proposed BSS-based approach is able to obtain a unified AA signal by exploiting the atrial information present in every ECG lead, which results in an increased robustness with respect to electrode selection and placement.
Atrial fibrillation is a very common cardiovascular disease in clinical practice. One relevant issue to understand its pathophysiological mechanisms is the analysis and interpretation of atrial electrograms (AEG). To study these signals properly, ventricular activity has to be removed from the AEG. In this work, a new application of independent component analysis (ICA) to the AEG is presented, where ventricular activity is removed from atrial epicardial recordings making use of only one reference lead. Therefore the technique is suitable when multi-lead recordings are unavailable as in atrial implantable cardioverter defibrilators. In addition to the proposed new methodology this work also presents the first comparative study, making use of unipolar epicardial AEGs, among the ICA-based technique, template matching and subtraction (TMS), and adaptive ventricular cancellation (AVC) on a database of 20 patients. A performance comparative analysis was carried out by evaluating epicardial atrial waveform similarity (S) and ventricular depolarization reduction (VDR) as a function of atrial rhythm regularity on a beat-by-beat basis. Results indicate that, when the epicardial atrial rhythm is quite organized, ICA is able to preserve the atrial waveform very precisely and better than the other methods (median S = 99.64% +/- 0.31% in contrast to 95.18% +/- 2.71% for TMS and 94.76% +/- 4.12% for AVC). Moreover, ventricular reduction is the best for ICA (median VDR = 6.32 +/- 4.41 dB in contrast to 4.98 +/- 4.48 dB for TMS and 4.12 +/- 2.72 dB for AVC). On the other hand, when the atrial activity is disorganized, TMS notably improves performance (S = 97.72% +/- 1.87%), but ICA still is the best in waveform preservation (S = 98.22% +/- 1.53%) whereas AVC remains similar (S = 93.74% +/- 4.38%). In conclusion, ICA can be considered as notably the best approach to reduce ventricular activity from unipolar atrial electrograms in organized atrial arrhythmias. On the other hand, both TMS and ICA give quite similar results when the atrial arrhythmia is disorganized.
Background:
The amplitude of bipolar electrograms (EGMs) is directionally sensitive, decreasing when measured from electrode pairs oriented oblique to a propagating wavefront.
Objective:
Use computational modeling 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 atrial fibrillation patients during pacing. For each EGM, the angle of incidence between the electrodes and the wavefront was measured using local conduction velocity (CV) mapping.
Results:
l A theoretical model was derived describing the effect of changing angle of incidence, electrode spacing, and CV on the local activation time (LAT) 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 LAT 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 (<5mm) it is predicted at all orientations.
Conclusions:
Directional sensitivity occurs because bipolar amplitude is reduced when 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.
Objectives:
This study aimed: 1) to determine the voltage correlation between sinus rhythm (SR) and atrial fibrillation (AF)/atrial flutter (AFL) using multielectrode fast automated mapping; 2) to identify a bipolar voltage cutoff for scar and/or low voltage areas (LVAs); and 3) to examine the reproducibility of voltage mapping in AF.
Background:
It is unclear if bipolar voltage cutoffs should be adjusted depending on the rhythm and/or area being mapped.
Methods:
High-density mapping was performed first in SR and afterward in induced AF/AFL. In some patients, 2 maps were performed during AF. Maps were combined to create a new one. Points of <1 mm difference were analyzed. Correlation was explored with scatterplots and agreement analysis was assessed with Bland-Altman plots. The generalized additive model was also applied.
Results:
A total of 2,002 paired-points were obtained. A cutoff of 0.35 mV in AFL predicted a sinus voltage of 0.5 mV (95% confidence interval [CI]: 0.12 to 2.02) and of 0.24 mV in AF (95% CI: 0.11 to 2.18; specificity [SP]: 0.94 and 0.96; sensitivity [SE]: 0.85 and 0.75, respectively). When generalized additive models were used, a cutoff of 0.38 mV was used for AFL for predicting a minimum value of 0.5 mV in SR (95% CI: 0.5 to 1.6; SP: 0.94, SE: 0.88) and of 0.31 mV for AF (95% CI: 0.5 to 1.2; SP: 0.95, SE: 0.82). With regard to AF maps, there was no change in the classification of any left atrial region other than the roof.
Conclusions:
It is possible to establish new cutoffs for AFL and/or AF with acceptable validity in predicting a sinus voltage of <0.5 mV. Multielectrode fast automated mapping in AFL and/or AF seems to be reliable and reproducible when classifying LVAs. These observations have clinical implications for left atrial voltage distribution and in procedures in which scar distribution is used to guide pulmonary vein isolation and/or re-isolation.
Aims:
Electroanatomical voltage mapping (EAVM) is an important diagnostic tool for fibrosis identification and risk stratification in non-ischaemic cardiomyopathy (NICM); currently, distinct cut-offs are applied. We aimed to evaluate the performance of EAVM to detect fibrosis by integration with whole heart histology and to identify the fibrosis pattern in NICM patients with ventricular tachycardias (VTs).
Methods and results:
Eight patients with NICM and VT underwent EAVM prior to death or heart transplantation. EAVM data was projected onto slices of the entire heart. Pattern, architecture, and amount of fibrosis were assessed in transmural biopsies corresponding to EAVM sites. Fibrosis pattern in NICM biopsies (n = 507) was highly variable and not limited to mid-wall/sub-epicardium. Fibrosis architecture was rarely compact, but typically patchy and/or diffuse. In NICM, biopsies without abnormal fibrosis unipolar voltage (UV) and bipolar voltage (BV) showed a linear association with wall thickness (WT). The amount of viable myocardium showed a linear association with both UV and BV. Accordingly, any cut-off to delineate fibrosis performed poorly. An equation was generated calculating the amount of fibrosis at any location, given WT and UV or BV.
Conclusion:
Considering the linear relationships between WT, amount of fibrosis and both UV and BV, the search for any distinct voltage cut-off to identify fibrosis in NICM is futile. The amount of fibrosis can be calculated, if WT and voltages are known. Fibrosis pattern and architecture are different from ischaemic cardiomyopathy and findings on ischaemic substrates may not be applicable to NICM.
Background:
Low-voltage-guided substrate modification is an emerging strategy in atrial fibrillation (AF) ablation. A major limitation to contemporary bipolar electrogram (EGM) analysis in AF is the resultant lower peak-to-peak voltage (Vpp) from variations in wavefront direction relative to electrode orientation and from fractionation and collision events. We aim to compare bipole Vpp with novel omnipolar peak-to-peak voltages (Vmax) in sinus rhythm (SR) and AF.
Methods and results:
A high-density fixed multielectrode plaque was placed on the epicardial surface of the left atrium in dogs. Horizontal and vertical orientation bipolar EGMs, followed by omnipolar EGMs, were obtained and compared in both SR and AF. Bipole orientation has significant impact on bipolar EGM voltages obtained during SR and AF. In SR, vertical values were on average 66±119% larger than horizontal (P=0.004). In AF, vertical values were on average 31±96% larger than horizontal (P=0.07). Omnipole Vmax values were 99.9±125% larger than both horizontal (99.9±125%; P<0.001) and vertical (41±78%; P<0.0001) in SR and larger than both horizontal (76±109%; P<0.001) and vertical (52±70%; P value <0.0001) in AF. Vector field analysis of AF wavefronts demonstrates that omnipolar EGMs can account for collision and fractionation and record EGM voltages unaffected by these events.
Conclusions:
Omnipolar EGMs can extract maximal voltages from AF signals which are not influenced by directional factors, collision or fractionation, compared with contemporary bipolar techniques.
Aims:
Identification of left atrial (LA) fibrosis through late gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) remains controversial due to the heterogeneity and lack of reproducibility of proposed methods. Our aim is to describe a normalized, reproducible, standardized method to evaluate LA fibrosis through LGE-CMR.
Methods and results:
Electrocardiogram- and respiratory-gated 3-Tesla LGE-CMR was performed in 10 healthy young volunteers and 30 patients with atrial fibrillation (AF): 10 with paroxysmal AF, 10 with persistent AF, and 10 with a previous AF ablation procedure. Local image intensity ratio (IIR) of the LA was calculated as the absolute pixel intensity to mean blood pool intensity ratio. The healthy atrial tissue threshold was defined in young healthy volunteers (upper limit of normality set at IIR tissue mean plus 2 SDs). Dense atrial scarring was characterized in patients with previous radiofrequency-induced scarring (post-AF ablation patients). Validation groups consisted of patients with paroxysmal and persistent AFs. The upper limit of normal IIR was 1.20; IIR values higher than 1.32 (60% of mean maximum pixel intensity in post-ablation patients) were considered dense scar. Image intensity ratio values between 1.2 and 1.32 identified interstitial fibrosis. Patients with paroxysmal and persistent AFs had less atrial fibrotic tissue compared with post-ablation patients. Endocardial bipolar voltage was correlated to IIR values.
Conclusions:
An IIR of 1.2 identifies the upper limit of normality in healthy young individuals. An IIR of >1.32 defines dense atrial fibrosis in post-ablation patients. Our results provide a consistent, comparable, and normalized tool to assess atrial arrhythmogenic substrate.
Unipolar electrogram can detect local as well as remote electrical activity of the heart. Information on how the amplitude and morphology of the recorded signal changes with the distance from the source tissue undergoing depolarization can help to better understand unipolar electrograms fractionation and provide insights into the passive conduction properties of the atrial tissue. Ten second unipolar atrial fibrillation (AF) electrograms were recorded using high-density electrode array from the posterior left atrium (LA) and right atrium (RA) of 19 (8 persistent - PERS & 11 paroxysmal - PAF) AF patients undergoing cardiac surgery. Conduction along lines of conduction block was detected in the recorded activation patterns by a proposed automated algorithm. Changes of the amplitude of the unipolar electrogram with increasing distance from the conduction blocks were assessed and compared to predictions of a theoretical model. For each recording, the median far-field decay space constant (FF0.5) was calculated. Overall, we found a significant difference between FF0.5 for patients with paroxysmal and persistent AF. Estimation of maximum FF0.5 from both RA and LA resulted in a mean FF0.5 of 1.5±0.2 mm for PERS patients and 2.1±0.6 mm for PAF patients (p=0.03). Moreover, detected conduction blocks demonstrated high spatial organization and appeared in distinctive areas of the mapped area in all patients, regardless of the type of AF, while the total number of detected block lines was higher in PERS patients.
Background:
The effects of varying the wavefront of activation on ventricular scar characterization has not been systematically assessed.
Methods and results:
Patients referred for ablation of scar-related ventricular tachycardia underwent voltage maps during a minimum of 2 wavefronts of activation. The bipolar and unipolar low-voltage areas were compared, and direct electrogram analysis was performed in regions where discrepancies were seen. Concordance between wavefronts was measured by calculating percentage of overlap between maps. Sixty endocardial voltage maps (360±147 points) were performed in 29 patients during 2 distinct wavefronts, with 3 wavefronts in 7 patients. With median bipolar and unipolar low-voltage areas of 37 and 116 cm(2), respectively, 22% and 14% variability in median scar area was observed with a different activation wavefront. Concordance between wavefronts was lower in patients with mixed scar compared to those with dense scar (52% [interquartile range, 29%-70%] versus 84% [interquartile range, 71%-87%]), with septal scars exhibiting the lowest concordance [(27% (interquartile range, 21%-56%)]. Among 16 critical sites for ventricular tachycardia, 3 (18%) were in a discordant region of scar, with one of the wavefronts showing voltage >1.5 mV.
Conclusions:
Significant differences in bipolar and unipolar low-voltage characterization of scar were observed with different ventricular activation wavefronts, particularly in septal locations and in patients without dense scar. In patients with a paucity of dense, low-voltage regions identified during substrate mapping, an alternate activation wavefront may increase the sensitivity to detect arrhythmogenic substrate and critical sites for ventricular tachycardia.
Background—
Complex-fractionated atrial electrograms and atrial fibrosis are associated with maintenance of persistent atrial fibrillation (AF). We hypothesized that pulmonary vein isolation (PVI) plus ablation of selective atrial low-voltage sites may be more successful than PVI only.
Methods and Results—
A total of 85 consecutive patients with persistent AF underwent high-density atrial voltage mapping, PVI, and ablation at low-voltage areas (LVA<0.5 mV in AF) associated with electric activity lasting >70% of AF cycle length on a single electrode (fractionated activity) or multiple electrodes around the circumferential mapping catheter (rotational activity) or discrete rapid local activity (group I). The procedural end point was AF termination. Arrhythmia freedom was compared with a control group (66 patients) undergoing PVI only (group II). PVI alone was performed in 23 of 85 (27%) patients of group I with low amount (<10% of left atrial surface area) of atrial low voltage. Selective atrial ablation in addition to PVI was performed in 62 patients with termination of AF in 45 (73%) after 11±9 minutes radiofrequency delivery. AF-termination sites colocalized within LVA in 80% and at border zones in 20%. Single-procedural arrhythmia freedom at 13 months median follow-up was achieved in 59 of 85 (69%) patients in group I, which was significantly higher than the matched control group (31/66 [47%], P <0.001). There was no significant difference in the success rate of patients in group I with a low amount of low voltage undergoing PVI only and patients requiring PVI+selective low-voltage ablation ( P =0.42).
Conclusions—
Ablation of sites with distinct activation characteristics within/at borderzones of LVA in addition to PVI is more effective than conventional PVI-only strategy for persistent AF. PVI only seems to be sufficient to treat patients with left atrial low voltage <10%.
Background—
The high incidence of postprocedural atrial tachycardia reduces the absolute arrhythmia-free success rate of extensive ablation strategies to treat nonparoxysmal atrial fibrillation (NPAF). We hypothesized that a strategy of targeting low-voltage zones and sites with abnormal electrograms during sinus rhythm (SR-AEs) in the left atrium after circumferential pulmonary vein isolation and cavotricuspid isthmus ablation in patients with NPAF is superior.
Methods and Results—
A total of 86 consecutive patients with NPAF were enrolled in study group. After circumferential pulmonary vein isolation, cavotricuspid isthmus ablation and cardioversion to SR, high-density mapping of left atrium was performed. Areas with low-voltage zone and SR-AE were targeted for further homogenization and elimination, respectively; 78 consecutive sex- and age-matched patients with NPAF who were treated with the stepwise approach served as the historical control group. In the study group, 92% (79/86) were successfully cardioverted after circumferential pulmonary vein isolation and cavotricuspid isthmus ablation. Among the patients converted to SR, 70% (55/79) had low-voltage zone and SR-AE and received additional ablation, whereas in 30% (24/79) without SR-AE or low-voltage zone, no further ablation was performed. During a follow-up period of >30 months, the Kaplan–Meier estimated probability to maintain SR at 24 months was 69.8% versus 51.3%. And after a single procedure, 3.5% (3/86) developed postprocedural atrial tachycardia in study group, compared with 30% (24/78) in control group ( P =0.0003).
Conclusions—
A strategy of selective electrophysiologically guided atrial substrate modification in SR after circumferential pulmonary vein isolation and cavotricuspid isthmus ablation is clinically more effective than the stepwise approach for NPAF ablation.
Clinical Trial Registration—
URL: http://clinicaltrials.gov . Unique identifier: NCT01716143.
Substrate mapping was developed to treat poorly tolerated infarct-related ventricular tachycardias (VTs). This concept was based on 30-year-old data derived from surgical and percutaneous mapping during sinus rhythm and VT that demonstrated specific electrograms (EGMs) that characterized the "arrhythmogenic substrate" of VT. Electrogram characteristics of the arrhythmogenic VT substrate during sinus rhythm included low-voltage, fractionation, long duration, split signals, and isolated late potentials as well as EGMs demonstrating adjacent early and late activation. Introduction of electroanatomical mapping (EAM) systems during the mid-1990s has allowed investigators to record electrograms in 3 dimensions and to identify sites assumed to represent the central common pathway ("isthmus") during re-entrant VTs. However, several important assumptions and misconceptions make currently used "substrate mapping" techniques inaccurate. These include: 1) re-entrant circuits are produced by fixed barriers of immutable "inexcitable" scar; 2) low voltage amplitude (≤&0.5 mV) implies dense "inexcitable" scar; 3) isthmuses identified in patients with tolerated VTs using entrainment mapping are both valid and provide an accurate depiction of isthmuses in less hemodynamically tolerated VTs; and 4) current mapping tools and methods can delineate specific electrophysiologic features that will determine the barriers forming channels during re-entrant VTs. None of these assumptions has been validated and recent experimental and human data using higher resolution mapping with very small electrodes cast doubt on their validity. These data call for re-evaluation of substrate-mapping techniques to characterize the arrhythmogenic substrate of post-infarction VT. Standardization of recording techniques including electrode size, interelectrode spacing, tissue contact, catheter orientation, and wavefront activation must be taken into consideration.
Background:
Catheter ablation strategies beyond pulmonary vein isolation (PVI) for treatment of atrial fibrillation (AF) are less well defined. Increasing clinical data indicate that atrial fibrosis is a critical common left atrial (LA) substrate in AF patients (pts).
Objective:
We applied a new substrate modification concept according to the individual fibrotic substrate as estimated from electroanatomic voltage mapping (EAVM) in 41 pts undergoing catheter ablation of AF.
Results:
First, EAVM during sinus rhythm was done in redo cases of 10 pts with paroxysmal AF despite durable PVI. Confluent low voltage areas (LVA) were found in all pts and were targeted with circumferential isolation, so-called box isolation of fibrotic areas (BIFA). This strategy led to stable sinus rhythm in 9/10 pts and was transferred prospectively to first procedures of 31 pts with non-paroxysmal AF. In 13 pts (42%), no LVA (<0.5mV) were identified, and only PVI was performed. In 18 pts (58%), additional BIFA strategies were applied (posterior box in 5, anterior box in 7, posterior plus anterior box in 5, no box in 1 due to diffuse fibrosis). Mean follow-up was 12.5±2.4months. Single-procedure freedom from AF/atrial tachycardia was achieved in 72.2 of pts and in 83.3 of pts with 1.17 procedures/patient.
Conclusions:
In approximately 40% of pts with non-paroxysmal AF, no substantial LVA were identified, and PVI alone showed high success rate. In pts with paroxysmal AF despite durable PVI and in approximately 60% of pts with non-paroxysmal AF, individually localized LVA were identified and could be targeted successfully with the BIFA strategy. This article is protected by copyright. All rights reserved.
Atrial disease or myopathy forms the substrate for atrial fibrillation (AF) and underlies the potential for atrial thrombus formation and subsequent stroke. Current diagnostic approaches in patients with AF focus on identifying clinical predictors with the evaluation of left atrial size by echocardiography serving as the sole measure specifically evaluating the atrium. Although the atrial substrate underlying AF is likely developing for years before the onset of AF, there is no current evaluation to identify the preclinical atrial myopathy. Atrial fibrosis is 1 component of the atrial substrate that has garnered recent attention based on newer MRI techniques that have been applied to visualize atrial fibrosis in humans with prognostic implications regarding the success of treatment. Advanced ECG signal processing, echocardiographic techniques, and MRI imaging of fibrosis and flow provide up-to-date approaches to evaluate the atrial myopathy underlying AF. Although thromboembolic risk is currently defined by clinical scores, their predictive value is mediocre. Evaluation of stasis via imaging and biomarkers associated with thrombogenesis may provide enhanced approaches to assess risk for stroke in patients with AF. Better delineation of the atrial myopathy that serves as the substrate for AF and thromboembolic complications might improve treatment outcomes. Furthermore, better delineation of the pathophysiologic mechanisms underlying the development of the atrial substrate for AF, particularly in its earlier stages, could help identify blood and imaging biomarkers that could be useful to assess risk for developing new-onset AF and suggest specific pathways that could be targeted for prevention.
© 2015 American Heart Association, Inc.
-The resolution of mapping is influenced by electrode size and interelectrode spacing. Smaller electrodes with closer interelectrode spacing may improve mapping resolution, particularly in scar. The aims of this study were to establish normal electrogram criteria in the atria for both 3.5mm electrode tip linear catheters (Thermocool®) and 1mm multielectrode-mapping catheters (Pentaray®) and to compare their mapping resolution in scar-related atrial arrhythmias.
-Normal voltage amplitude cutoffs for both catheters were validated in 10 patients with structurally normal atria. In 20 additional patients with scar-related atrial arrhythmias, similar sequential mapping with both catheters was performed. Normal bipolar voltage amplitude was similar between 3.5mm and 1mm electrode catheters with a 5(th) percentile of 0.48mV and 0.52mV, respectively (p=0.65). In patients with scar-related atrial arrhythmias, the total area of bipolar voltage <0.5mV measured using 1mm electrode catheters was smaller than that measured using 3.5mm catheter (14.7cm(2) vs 20.4cm(2); p=0.02). The mean bipolar voltage amplitude in this area of low voltage was significantly higher with 1mm electrode catheters (0.28mV and 0.17mV, p=0.01). Importantly, 54.4% of all low voltage data points recorded with 1mm electrode catheter had distinct electrograms that allowed annotation of local activation time compared with only 21.4% with 3.5mm electrode tip catheters (p=0.01). Overdrive pacing with capture of the tachycardia from within the area of low voltage was more frequent with 1mm electrode catheters (66.7 vs 33.4; p=0.01).
-Mapping with small closely spaced electrode catheters can improve mapping resolution within areas of low voltage.
Intracardiac electrograms are an indispensable part during diagnosis of supraventricular arrhythmias, but atrial activity (AA) can be obscured by ventricular far-fields (VFF). Concepts based on statistical independence like principal component analysis (PCA) cannot be applied for VFF removal during atrial tachycardia with stable conduction.
A database of realistic electrograms containing AA and VFF was generated. Both PCA and the new technique periodic component analysis (πCA) were implemented, benchmarked, and applied to clinical data.
The concept of πCA was successfully verified to retain compromised AA morphology, showing high correlation (cc=0.98±0.01) for stable atrial cycle length (ACL). Performance of PCA failed during temporal coupling (cc=0.03±0.08) but improved for increasing conduction variability (cc=0.77±0.14). Stability of ACL was identified as a critical parameter for πCA application. Analysis of clinical data confirmed these findings.
πCA is introduced as a powerful new technique for artifact removal in periodic signals. Its concept and performance were benchmarked against PCA using simulated data and demonstrated on measured electrograms.
Copyright © 2015 Elsevier Inc. All rights reserved.
In humans, the existence of rotors or reentrant sources maintaining AF and the underlying electroanatomic substrate has not been well defined.
Our objective was to determine the prevalence of localized rotational activation (RotA) in the left atrium (LA) during human AF and whether CFAEs or low voltage areas co-localize with RotA sites.
We prospectively studied 32 patients (57±8yrs, 88% persistent AF) undergoing AF catheter ablation. Bipolar EGMs were recorded for 2.5sec during AF using a roving 20-pole circular catheter in the LA. RotA was defined as sequential temporal activation of bipoles around the circular catheter. Bipolar EGM fractionation index and bipolar voltage were used to define CFAEs and low voltage areas, respectively.
In 21 (66%) patients, 47 RotA sites were identified. Few (9%) lasted 2.5sec (CL 183±6ms), while the majority (91%) were nonsustained (duration 610±288ms, CL 149±11ms). RotA was most common in the PV antrum (71%) and posterior LA (25%). CFAEs were recorded from 18±12% of LA area and most (92±7%) were not associated with RotA sites. However, 85% of RotA sites contained CFAEs. Very low voltage (<0.1mV) areas comprised 12±10% of LA area and were present in 23% of RotA sites.
In patients with predominantly persistent AF, localized RotA is commonly present, but tends to be transient (<1 second). Although most CFAEs do not co-localize with RotA sites, the high prevalence of CFAEs and very low voltages within RotA sites may indicate slow conduction in diseased myocardium necessary for their maintenance.
Laplacian Electrograms and Ventricular Fihrillation. Introduction. During ventricular fibrillation (VF) interpretation of a local electrogram and determination of the local activation moment are hampered by remote activity or intervening repolarization waves. Successful defibrillation depends on critical timing of the shock relative to local activation. We tested the applicabillity of Laplacian electrograms for detection of the moment of local activation during VF.
Methods and Results. From isolated perfased porcine infact heart, 247 local unipolar electrograms were recorded simultaneously (13 × 19 matrix, interelectrode distance 0.3 mm) from the left ventricular wall during sinus rhythm, following pacing or during VF, Activation maps were constructed based on local unipolar electrograms, and Laplacian electrograms were calculated from local electrograms ane its eight neighbors. The Laplacian electrogram displayed a sharp R/S complex with local activation iodicted by the moment of zero crossing without interference from remote activity or repolarization waves. Its amplitude increased with decreasing interelectrode distance, Following epicardial stimulation, Laplacian amplitude was significantly larger than during complexes with different morphology. Collision of wavefronts was associated with entirely positive Laplacian waveforms; “focal” appearancce of acitivity was associated with an entirely negative waveform. Activation block in the activation maps was correlated with the appearance of substanined episodes of negativity or positivity in the Laplacian electrogram (depending on the location of the recording site relative to the line of block).
Conclusion. Laplacian electrograms allow detection of the moment of local activation without interference from remote activity or repolarization, especially during complex arrhythmias. The technique applied toe automatic sensing devices, such its the internal defibrillator, may optimize defibrtilation success. (J Cardiovasc Electrophysiol, Vol. 11, pp. 1119-1128, October 2000)
During ventricular fibrillation (VF), interpretation of a local electrogram and determination of the local activation moment are hampered by remote activity or intervening repolarization waves. Successful defibrillation depends on critical timing of the shock relative to local activation. We tested the applicability of Laplacian electrograms for detection of the moment of local activation during VF.
From isolated perfused porcine intact hearts, 247 local unipolar electrograms were recorded simultaneously (13 x 19 matrix, interelectrode distance 0.3 mm) from the left ventricular wall during sinus rhythm, following pacing or during VF. Activation maps were constructed based on local unipolar electrograms, and Laplacian electrograms were calculated from local electrograms and its eight neighbors. The Laplacian electrogram displayed a sharp R/S complex with local activation indicated by the moment of zero crossing without interference from remote activity or repolarization waves. Its amplitude increased with decreasing interelectrode distance. Following epicardial stimulation, Laplacian amplitude was significantly larger than during a breakthrough pattern. During VF, identical unipolar electrograms corresponded to Laplacian complexes with different morphology. Collision of wavefronts was associated with entirely positive Laplacian waveforms; "focal" appearance of activity was associated with an entirely negative waveform. Activation block in the activation maps was correlated with the appearance of sustained episodes of negativity or positivity in the Laplacian electrogram (depending on the location of the recording site relative to the line of block).
Laplacian electrograms allow detection of the moment of local activation without interference from remote activity or repolarization, especially during complex arrhythmias. The technique applied to automatic sensing devices, such as the internal defibrillator, may optimize defibrillation success.
This paper considers a quantitative description of intracellular and transmembrane currents in anisotropic muscle, with emphasis on the factors that determine the extracellular potentials. Although Vmax of the intracellular action potential had no relation to changes in conduction velocity in anisotropic tissue with constant membrane properties, the extracellular waveforms were quite sensitive to velocity changes. Large amplitude biphasic deflection occurred in the fast areas, and in the slow areas the waveforms were of lower amplitude and triphasic in shape; i.e., negative potentials preceded the biphasic positive-negative deflection. The extracellular potentials were simulated on the bases of a model of intracellular currents, and the theoretical and measured results showed good agreement. In tissue with anisotropic conductivity, the relationship between the spatial intracellualr potential gradient and the magnitude of the extracellular potential of the excitation wave was opposite to the classical relationship in isotropic tissue. Due to the influence of the effective intracellular conductivity on the spread of intracellular currents and on conduction velocity, in anisotropic tissue the extracellular potential decreased as the intracellular potential gradient increased. The peak values of the positive and negative potentials and the spatial distribution of the potential gradients varied considerably along the activation front. These findings were accounted for by differences in the distribution and spatial extent of the transmembrane currents, which were determined by the intracellular currents. The theoretical analysis showed that intracellular and transmembrane currents were proportional to the local conduction velocities of the wavefront. Thereby, it was not possible to have a "uniform layer" of current when there were differences in conduction velocity along the length of the excitation wave. The implications of the analysis are considerable, since the gratifying agreement between the theoretical and measured results indicates that the details of the extracellular waveforms can be explained on the basis of the distribution of intracellular currents; i.e., extracellular potentials provide a sensitive index of intracellular current flow.
The goal of this study was to assess the impact of left atrial scarring (LAS) on the outcome of patients undergoing pulmonary vein antrum isolation (PVAI) for atrial fibrillation (AF).
Left atrial scarring may be responsible for both the perpetuation and genesis of AF.
A total of 700 consecutive patients undergoing first-time PVAI were studied. Before ablation, extensive voltage mapping of the left atrium (LA) was performed using a multipolar Lasso catheter guided by intracardiac echocardiography (ICE). Patients with LAS were defined by a complete absence of electrographic recording by a circular mapping catheter in multiple LA locations, and this was validated by electroanatomic mapping. All four pulmonary vein antra and the superior vena cava were isolated using an ICE-guided technique. Patients were followed at least nine months for late AF recurrence. Univariate and multivariate analyses were performed to assess the predictive value of LAS and other variables on outcome.
Of 700 patients, 42 had LAS, which represented 21 +/- 11% of the LA surface area by electroanatomic mapping. Patients with LAS had a significantly higher AF recurrence (57%) compared with non-LAS patients (19%, p = 0.003). Also, LAS was associated with a significantly larger LA size, lower ejection fraction, and higher C-reactive protein levels. Univariate analysis revealed age, nonparoxysmal AF, and LAS as predictors of recurrence. Multivariate analysis showed LAS as the only independent predictor of recurrence (hazard ratio 3.4, 95% confidence interval 1.3 to 9.4; p = 0.01).
Pre-existent LAS in patients undergoing PVAI for AF is a powerful, independent predictor of procedural failure. Left atrial scarring is associated with a lower EF, larger LA size, and increased inflammatory markers.
Dominant frequency (DF) analysis of atrial electrograms has been used to characterize atrial fibrillation (AF). The aim of this study was to explore technical issues that may affect the estimation of local activation rate during AF using DF analysis.
Epicardial atrial electrograms recorded during AF from 10 dogs were used to evaluate the effects of unipolar versus bipolar recordings, bipolar electrode spacing, postrecording processing, far field ventricular depolarizations, ventricular template subtraction, and signal duration on DF analysis. Simulated electrograms were used to evaluate the effect of far field ventricular depolarizations and signal-to-noise ratio. DFs were compared with activation rates obtained by manual marking and the reproducibility of the DFs was evaluated. Bipolar electrograms were found to be preferable to unipolar electrograms. Preprocessing was a necessary step for bipolar signals, but also aided analysis of unipolar recordings. Ventricular far field depolarizations significantly affected DFs. Ventricular template subtraction helped DF analysis in signals with both minimal and significant ventricular components. A recording duration above 2 seconds was required for reliable DF measurements. Signal-to-noise ratios below 13 dB could also affect DF, particularly for signals with significant amplitude and frequency variation.
Various factors affect DF analysis. Proper interpretation of DF analysis requires careful evaluation of the AF signals and robust processing techniques.