Non-invasive cardiac mapping in clinical practice: Application to the ablation of cardiac arrhythmias

Available online at www.sciencedirect.com

ScienceDirect Journal of Electrocardiology xx (2015) xxx – xxx www.jecgonline.com

Non-invasive cardiac mapping in clinical practice: Application to the ablation of cardiac arrhythmias Rémi Dubois, PhD,⁎ Ashok J. Shah, MD, Mélèze Hocini, MD, PhD, Arnaud Denis, MD, Nicolas Derval, MD, Hubert Cochet, MD, PhD, Frédéric Sacher, MD, PhD, Laura Bear, PhD, Josselin Duchateau, Msc, Pierre Jais, MD, PhD, Michel Haissaguerre, MD, PhD IHU LIRYC, Electrophysiology and Heart Modeling Institute, Fondation Bordeaux Université, France Hopital de Cardiologie du Haut Lévêque, CHU de Bordeaux, France Université de Bordeaux, INSERM U1045, CRCTB, France

Abstract

Ten years ago, electrocardiographic imaging (ECGI) started to demonstrate its efficiency in clinical settings. The initial application to localize focal ventricular arrhythmias such as ventricular premature beats was probably the easiest to challenge and validates the concept. Our clinical experience in using this non-invasive mapping technique to identify the sources of electrical disorders and guide catheter ablation of atrial arrhythmias (premature atrial beat, atrial tachycardia, atrial fibrillation), ventricular arrhythmias (premature ventricular beats) and ventricular pre-excitation (Wolff–Parkinson–White syndrome) is described here. © 2015 Elsevier Inc. All rights reserved.

Keywords:

Non-invasive mapping; Cardiac arrhythmia; ECGI

Introduction A recently developed, ECG-based, three dimensional (3D) electrocardiomapping modality named electrocardiographic imaging (ECGI) has refined non-invasive diagnosis of heart rhythm disorders [1–3]. Our clinical experience in using this non-invasive mapping technique to identify the sources of electrical disorders and guide catheter ablation of atrial arrhythmias (premature atrial beat, atrial tachycardia, atrial fibrillation), ventricular arrhythmias (premature ventricular beats) and ventricular pre-excitation (Wolff–Parkinson– White syndrome) is described below.

Mapping technique A vest embedded with 252 electrodes is applied to the patient's torso and connected to the non-invasive system which records 252 unipolar electrocardiograms. A non-contrast thoracic CT scan obtains high-resolution images of the heart and the vest electrodes. The 3D epicardial bicameral (atria or/and ventricles) geometries are reconstructed from segmental CT images (Fig. 1). The relative positions of body surface electrodes can be visualized on the torso geometry. ⁎ Corresponding author at: IHU LIRYC, PTIB, Hopital Xavier Arnozan, 33604 Pessac Cedex, France. E-mail address: [email protected] http://dx.doi.org/10.1016/j.jelectrocard.2015.08.028 0022-0736/© 2015 Elsevier Inc. All rights reserved.

The mapping system solves for an ‘inverse solution’ to reconstruct epicardial potentials (ECVue™, CardioInsight Technologies Inc., Cleveland, OH), unipolar electrograms, and activation maps from torso potentials for at least one beat/cycle using mathematical reconstruction algorithms [2,4].

Atrial arrhythmias Atrial fibrillation In the area of atrial fibrillation (AF), noninvasive ECG mapping facilitates catheter ablation by contributing to our understanding of AF pathophysiology. Currently, pulmonary vein (PV) isolation remains the cornerstone of catheter ablation for AF [5]. Recently, there is emerging evidence that AF may be driven and maintained by localized reentrant and focal sources in the atria [6–8]. Mapping dynamic localized AF sources proved to be difficult using single point catheters, regional multielectrode catheters [7], or surgical plaques [6] and remained limited due to several factors, such as the inability to map both atria simultaneously, catheter contact issues, and limited surgical access [9]. With the advent of noninvasive mapping, AF is mapped beat-to-beat in a panoramic fashion, allowing for the identification of potential driving sources [10,11].

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R. Dubois et al. / Journal of Electrocardiology xx (2015) xxx–xxx ~1 hour

Vest positioning

CT Scan

Recording in the EP Lab SemiAutomatic Segmentation Recording in the patient’s room

Fig. 1. Workflow for ECGI mapping.

Non-invasive mapping approach Atrial cardiac potentials are much finer compared to ventricular potentials. To noninvasively map the atria accurately, several key barriers need to be overcome [9,11,12]. Consecutive windows with R-R pauses longer than 1000 ms during AF are analyzed. To avoid QRST interference, only the T-Q segments are selected for analysis. In patients with rapid ventricular rates, diltiazem may be administered to slow atrioventricular (AV) conduction in order to create adequate recording windows [11]. Filtering processes are applied to remove artifacts in signal morphology [9,10].

Activation maps are computed utilizing the intrinsic deflection-based method on unipolar electrograms (−dV/dTmax) [9,11,12]. Phase mapping algorithms can be applied to reconstructed global atrial signals to create AF maps, a representation of the wavefront is computed from the isophase values corresponding to π/2 [11]. Movies of wave propagation patterns are then displayed on the biatrial geometry individualized for each patient. With the above technique, two general types of AF drivers have been identified: (1) reentrant, when a wave is observed to fully rotate around a functional core on phase progression; and (2) focal, when a wavefront originates from

Fig. 2. Phase mapping showing posterior view of left atrium during paroxysmal AF. Panel A shows serial snapshots of a single wave emerging out of the left inferior PV (white star) and reaching right veins in 30 ms while it expands radially to the roof and inferior walls. Panel B shows serial snapshots of two successive rotations (white arrows) of a rotor located near the ostia of right veins. The core of the rotor (white star at the center of rainbow-colored phases of rotor) is seen meandering in a small region in this example. The blue wave indicates the depolarizing front, which makes one full rotation in 160 ms. The phases of wave propagation are color-coded using rainbow scale. The blue color represents depolarizing wave and the green represents the end of repolarization. The wavefront can be read by following the blue color. The time (ms) at the bottom of each snapshot represents the moment in the time-window when the snapshot was taken. Abbreviations: LSPV, left superior pulmonary vein; LIPV, left inferior PV; RSPV, right superior PV; RIPV, right inferior PV, SVC, superior vena cava. From Haissaguerre et al. [10], with permission.

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a focal site with centrifugal activation (Fig. 2). To describe the meandering nature of reentrant drivers observed in AF, the CT-based biatrial geometry is divided into regional domains [11]. An aggregated driver-density map computed from a mean cumulative map time of 9 +/− 1 seconds is then created that cumulates all the drivers recorded in each window and is projected on the patient's biatrial geometry; a mean value of.

Paroxysmal AF We mapped 23 consecutive patients with clinical paroxysmal AF non-invasively to guide catheter ablation. The invasive procedure consisted of a mapping with a multi-electrode catheter (PentaRay, Biosense Webster) at sites of non-invasively identified sources and RF application at these target sites with the endpoint of AF termination (ie conversion into sinus rhythm or tachycardia). Noninvasive maps showed single or repetitive discharges from one or several pulmonary veins, coexisting with rotor drifting along the venous ostia in the posterior wall. The pulmonary vein discharges either extinguished or reset a pre-existing rotor. The rotor was not temporally stationary for more than mean 2 rotations. The anterior left as well as the right atrium were activated passively by the left atrial waves travelling over the Bachman's bundle or the coronary sinus or both. In total, 657 drivers were mapped in 23 patients (512 rotors (77.9%) and 145 PV discharges/foci (22.1%)). The LA harbored the majority of arrhythmogenic events: 89% of the re-entrant drivers and 75% of foci. The first ablated PV region terminated AF in 9 patients (and prolonged AF cycle length in 30%). The second targeted PV region terminated AF in an additional 8 patients. The remaining 6 patients achieved AF termination on ablating the 3rd or 4th targeted non-PV regions. Later, circumferential PV isolation was undertaken and achieved in all patients. The findings of non-invasive mapping reinforces the arrhythmogenic role of PVs in paroxysmal AF. The posterior left atrial PV regions are the most frequent (N 80%) ablation target sites leading to termination of paroxysmal AF which is in concurrence with the key role of PVI in AF ablation [13].

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Persistent AF In persistent AF, the identification of AF drivers helps pin point the targets for substrate ablation. In the recent study [11], 103 consecutive patients undergoing catheter ablation for persistent AF were investigated using noninvasive phase mapping. A median of 4 driver regions was identified in patients with persistent AF. Of the recorded driver activity, 80.5% were reentrant and 19.5% were focal. Reentrant AF drivers were commonly located in the right PV/septal region, left PV/LA appendage region, left inferior wall/coronary sinus region and the superior right atrium; however, the exact locations varied amongst individuals. Reentrant activity was noted to be not sustained, with the median number of continuous rotations being 2.6 (interquartile range 2.3,3.3) lasting for mean duration of 449 ± 89 ms, but would often recur at the same or adjacent site. On the other hand, an average of 6 focal discharges was noted from a focal site. In a subset of patients in this study, electrogram characteristics of AF driver versus non-driver regions were compared using an invasive multielectrode catheter. Regions harboring reentrant AF drivers more often demonstrated prolonged fractionated electrograms, and the recorded electrograms spanned across a large part of the AF cycle length. Studies are underway to delineate the electrogram characteristics of these reentrant activities. However, fractionation alone is non-specific, as it can be influenced by contiguous anatomical structures, slow or anisotropic conduction, and the direction or overlap of multiple wavefronts. A previous study however, has indicated that these reentrant drivers tended to harbor in the patchy zones bordering dense fibrotic areas [14–17]. The aggregated driver-density map derived from noninvasive mapping serves as a roadmap for ablation. Point-bypoint lesions are applied at the area harboring reentrant or focal drivers, starting with the region of highest driverdensity and proceeding in a decreasing order. Local cycle length slowing is pursued as an endpoint of regional ablation, where initial electrograms are often rapid and fractionated. They are targeted until they become slower and less complex (Fig. 3) usually harboring synchronous activation on distal and proximal electrodes of the ablation catheter (indicative of passive activation) (Fig. 4).

Cycle length = 120ms

Fig. 3. Upper and middle panel: The endpoint of local ablation is increase in local cycle length and transformation of rapid and complex signals into simple and slower local rhythm. Lower panel: It is not desirable to achieve complete electrogram abolition locally which results in tissue scarring post ablation.

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A

C

B

Fig. 4. A 67-year-old male with 1-month-long persistent AF. (A) Focal map from ECGi pre-ablation; the number of focal discharges are shown for each location. (B) Reentrant driver map. The driver regions from ECGi are shown in red. The marked regions are: left appendage, left septum, ostia of the right veins and inferior left atrium. (C): CartoTM map of the anterior left atrium showing tags of ablation involving focal breakthroughs at the junction of left veins and appendage, the site of AF termination. Also shown are the ablation tags (red dots) on the left septum corresponding to the region of septal reentrant drivers which are projected anteriorly on the biatrial geometry shown in the left panel. The relatively low density of (real time) ablation tags is sufficient to achieve the local endpoint, here.

Using this approach, AF was acutely terminated in 80% of patients. The number of driver regions targeted to achieve AF termination increased with the duration of persistent AF; a single dominant region was identified in only 9% of patients. Fig. 5 shows a typical record form of ablation procedure and Fig. 6 shows an interesting correlation with conventional ECG of fibrillatory waves. Among 90 patients who completed 12-month follow-up, 64% of patients were in stable sinus rhythm (SR), 22% in AT and 20% in AF [11]. Importantly, the strategy of driver-based ablation guided by noninvasive mapping achieved similar 12-month clinical outcomes to the conventional stepwise approach, but with half the amount of ablation (28 vs. 65 minutes for AF termination) [11]. In this setting, persistent AF ablation guided by noninvasive mapping of localized drivers offers the ability to direct therapy to localized AF driver regions, and the potential to minimize the extent of ablation. Atrial premature complex and atrial tachycardia We have prospectively mapped and ablated various clinical ATs [18] in a wide range of patients using the non-invasive tool to 1) define the mechanism of AT: macroreentrant

(perimitral, cavotricuspid isthmus-dependent and roofdependent circuits) vs. centrifugal focal activation and 2) locate the source of arrhythmia in centrifugal ATs (Fig. 7). Fifty-two patients (age: 61 ± 11 years; 42 male, structural heart disease in 18) with clinical AT (mean cycle length 284 ± 85 ms) including those arising de novo, after catheter or surgical AF ablation (N = 27) and post-atriotomy were included from three world centers [18]. All patients were first mapped bedside non-invasively, followed median 1 day (interquartile range: 1, 7) later by invasive mapping and ablation. The invasive operator was blinded to the non-invasive diagnosis. Invasive electrophysiological mapping was performed using conventional electrogram and 3D electroanatomical mapping system guidance. Non-invasive map was considered accurate when its diagnosis matched the invasive mapping and was subsequently confirmed by successful ablation. The non-invasive diagnoses were evaluable in 48 of 52 patients. In four patients, clinical AT converted to another rhythm (AT and AF in 1 each and sinus in 2) before invasive mapping was completed, and therefore, these patients were excluded from the comparative analysis. Out of 48 evaluable clinical ATs, 27 ATs were diagnosed in the EP laboratory as macroreentrant and 21 as centrifugal arrhythmias. All of them were successfully terminated by ablation resulting in sinus rhythm in 44 or another AT in 4.

R. Dubois et al. / Journal of Electrocardiology xx (2015) xxx–xxx Targets:

5

# Rotors

# Focals

RF Time

LAA CL

RAA CL

AF Term?

1-Septum

43

3

8

217

232

no

2-Inferior LA

21

0

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238

238

no

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10

29

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CS organization

4-RAA

11

3

5

248

248

AF term in AT

Target 3

Target 4 AP

Target 2 Target 3 Target 3 Target 1 Target 4

Reentries

Focal Breakthroughs

Fig. 5. In a 68-year-old male with persistent AF of 7 months, the AF-driver record-form notes septum, inferior left atrium, left and right appendages as ablation target sites in sequence from 1 to 4 after more than 28 seconds of AF was analyzed. (A) The number of rotors and focal breakthroughs, RF ablation time, appendage cycle lengths and the endpoint/outcome of ablation are tabulated for each target site. AF terminated to AT during ablation of 4th target site (right appendage). Total RF time to achieve AF termination is 23 minutes. Below, the corresponding biatrial images show reentrant drivers (B) (number of rotations of the reentrant drivers are represented by digits on the map) and focal breakthroughs (C).

The overall diagnostic accuracy compared to invasive EP diagnosis, the gold standard, was 92% (100% in patients without any previous ablation and 83% in patients with previous AF ablation(s)). Non-invasive mapping was particularly useful and adept at accurately diagnosing centrifugal ATs (100% success rate including 11 (58%) patients with previous AF ablation). In this study, the primary reason of failure to diagnose the arrhythmia mechanism in 4 out of 48 (8%) evaluable ATs was 2:1 atrio-ventricular conduction, precluding the selection of a full tachycardia cycle that is not contaminated by a QRST complex which is necessary for single cycle analysis. This can be addressed clinically by administration of atrioventricular node blockers or simple pacing maneuvers during the invasive procedure to unmask multiple P waves. In addition, some post-ablation atria exhibited substantially lower-ECG P-wave amplitude which further complicated and challenged the diagnosis, contributing to lower accuracy in post AF ablation ATs (83%). Noise reduction using a signal-averaging algorithm is being investigated with promising initial results to improve the accuracy in low voltage substrate [18]. A potential limitation of the system is its inability to provide direct mapping of the septum. Since the septum is not an epicardial structure and therefore not included or displayed on the map, a septal source is deduced by demonstrating simultaneous activation of both chambers from the inter-atrial groove. While precise localization on the septum may not be feasible for septal-source ATs, the deductive information may suffice with regard to ablation of target in the region of interest. Although there is evidence for

differential activation of the contiguous endo-epicardium in the atria (in at least some of its parts), the difference, at best, could be considered modest considering that the atrial tissue is much thinner in most parts than the ventricular myocardium.

Ventricular arrhythmias Ventricular premature complex and ventricular tachycardia Premature ventricular complexes (PVCs) or outflow tract ventricular tachycardias (VTs) are commonly encountered in clinical practice [19]. Localizing the origin of these arrhythmias can be challenging in cases that occur infrequently or last transiently (i.e., few beats). In this scenario, noninvasive mapping may be particularly useful [19,20]. The use of noninvasive mapping to localize PVCs has been validated by electrophysiological studies [19,21]. In a study by Jamil-Copley et al. [19], patients wore a body vest consisting 252-surface electrodes for noninvasive localization of these ventricular arrhythmias. Patients were allowed to ambulate and the vest was applied up to 5 hours prior to the procedure to capture the culprit arrhythmia. Cardiac potentials, activation maps and voltage maps were derived from noninvasive mapping. Noninvasive mapping successfully identified the outflow tract ventricular tachycardia/PVC origin in 96% of cases, correctly sublocalizing to specific areas in the right or left outflow tract. Acute success was achieved in 100% of patients and medium success was achieved in 92% of patients.

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Pre-ablation

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RAA CL

204

233

Inferior LA

25

0

7

214

235

LA septum

11

0

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-

-

AF Term

no AF term in SR

Fig. 6. In a 67-year-old male, 5-month-persistent AF with baseline left appendage cycle length of 172 ms terminated after ablation of inferior left atrial followed by left septal region in 11 minutes. The two arrhythmogenic regions are displayed on panels A and B. The corresponding fibrillatory waves display concordant features in inferior ECG leads. (A) Inferior left atrium appears as the driver region during AF with negative f waves in II, III, and F. (B) Septal region appears as the driver during AF with positive f waves in II, III, and F. (C) Quantitative results of the ECGi, time of radio-frequency applied, and left (resp. right) appendage cycle length after ablation.

Erkapic et al. [22] studied the non-invasive technique in comparison with routine clinical mapping of monomorphic PVCs with or without monomorphic VT. Forty-two patients were enrolled prospectively and randomized into two groups: ventricular ectopy localization using either 12-lead ECG algorithms or non-invasively with EcVue™ (CardioInsight Technologies, Cleveland, OH) followed by conventional guided ablation. The EcVue™ system accurately identified both the chamber and sub-localized the PVC origin in 20 of 21 (95.2%) patients. In contrast, using 12-lead ECG algorithms, the chamber was accurately diagnosed in 16 of 21 (76.2%) patients, while the arrhythmia origin in only 8 of 21 (38.1%) (P = 0.001 vs. EcVue™). Acute success in ablation was achieved in all patients. Regarding the number of radiofrequency-energy applications (in total 2 vs. 4, P = 0.005) in the EcVue™ arm, ablation was more precise than in the ECG group which used standard-of-care activation and pace mapping-guided ablation. Three months success in ablation was 95.2% for the EcVue™ and 100% for the ECG group (P = ns). Time to ablation was 35.3 min in the conventional arm and 24.4 min in ECVUE™ group (P = 0.035). The X-ray radiation exposure was 3.21 vs. 0.39 mSv (P = 0.001 for the EcVue™ group and ECG group, respectively). The

authors concluded that non-invasive technology offers higher accuracy and more targeted ablation of PVCs superior to the 12-lead ECG but has significantly higher radiation exposure due to computed tomography scan. In another multicenter study, 35 premature ventricular beats imaged non-invasively were accurately diagnosed in 100% patients with regard to chamber identification and focal mechanism (Fig. 8, top) [23]. Ventricular pre-excitation Ghosh et al. [24] imaged 14 pediatric patients with Wolff–Parkinson–White syndrome and no other congenital disease, with ECG imaging a day before catheter ablation. The preexcitation sites were consistent with sites of successful ablation (5 left lateral, 4 left posteroseptal, 2 right posteroseptal, 1 right mid-septal, 1 right posterior and 1 in the coronary sinus diverticulum), qualitatively, in all cases to within a 1-hour arc of each atrioventricular annulus. In a patient with two closely-situated accessory pathways, ECG imaging showed two contiguous epicardial breakthroughs. Based on the electrogram morphology (QS vs rS patterns), non-invasive maps could differentiate between the endocardial (12) and epicardial (2) locations of the accessory pathways.

R. Dubois et al. / Journal of Electrocardiology xx (2015) xxx–xxx

7

A B C

ms 0

20

40

60

Fig. 7. ECG (A) and isochronal map (B) of a focal paroxysmal AT arising from the anterior wall of the right superior pulmonary venous ostium (ecVue, CardioInsight Tech.) The AT was successfully ablated at the corresponding site seen on the fluoroscopic image (C). AT terminated after 9 seconds of radiofrequency application. Abbreviations: IVC, inferior vena cava; SVC, superior vena cava; RAA, right atrial appendage; LAA, left atrial appendage.

Ghosh et al. also reported qualitatively accurate EGM imaging of accessory pathways observed in patients with structurally abnormal hearts like hypertrophic cardiomyopathy, Ebstein's anomaly and status post repair of a univentricular heart [25,26]. In another multicenter study, 7 patients with Wolff– Parkinson–White syndrome imaged non-invasively were accurately diagnosed with regard to the identification of the ventricular epicardial breakthrough site of preexcitation (delta) wave (Fig. 8, bottom) [27]. Cakulev et al. reported six patients with WPW syndrome including four with ECGs suggestive of a septal ventricular insertion of the accessory pathway based on 12 lead ECG based algorithms [21,28]. In all of these patients, the ECG was indeterminate as far as whether the ventricular insertion was on the left or right side of the ventricular septum. ECGI accurately predicted the ventricular insertion of the pathway in the left or the right ventricle, which was confirmed by the invasive mapping. One of these four patients had an epicardial insertion of the pathway that was accurately identified by ECGI. We have used the same system in patients with WPW who had previously failed multiple ablations (endocardial and epicardia). The system enabled the localization of accessory pathways in unusual locations like diverticulum of right appendage and underneath the junction of right and non-coronary aortic cusps followed by successful ablation endocardially [29,30].

tricular complexes (24 PVCs), focal atrial tachycardias (2 ATs) and manifest accessory pathways (7 WPW syndromes) were prospectively explored for the location of origin of the focal arrhythmia, non-invasively. Subsequently, a stimulus artifact was delivered with the catheter steered to the site of focal-source to confirm and evaluate the precise location of the mapped focal origin. The procedural parameters and clinical efficacy were studied. Ablation was successful in 32/33 (97%) patients (PVCs: 13 right, 10 left, 1 septal; WPW: 3 left, 3 right; ATs: 2 left) without complications. The time from catheterization to permanent arrhythmia elimination/termination, RF duration, skin-to-skin procedural duration and fluoroscopic exposure were median 16 min, 3.98 min, 71 min and 11.9 min (for n = 29) respectively. At a mean of 24.7 ± 3.7 months of follow-up, 31 patients remain arrhythmia-free after a single procedure. One patient (right WPW syndrome) required repeat ablation 1 month later. One patient had recurrence of PVCs and is now deceased. The cumulative radiation (CT scan and fluoroscopy) exposure was median 7.57 mSv. The study concluded that catheter-based treatment of premature ventricular beats, manifest accessory pathways and atrial tachycardias can be expedited under the sole guidance of bedside, pre-procedural, non-invasive, diagnostic maps. Of note, the arrhythmia elimination could be achieved successfully without the need for invasive mapping in 97% patients in less than 30 seconds from the onset of first RF application.

Rapid mapping

Conclusion

In a multi-center European study [31], 33 patients (mean age 45.0 ± 14.6 years) with symptomatic premature ven-

Various atrial and ventricular arrhythmias including complex fibrillatory processes can be mapped non-invasively

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A

LAO

LAD MV

PA

TV

B Ao

MV TV

Fig. 8. (A) Biventricular isopotential map (yellow color denotes the earliest activation) during premature ventricular complex (12-lead ECG). Inserted is an epicardial virtual electrogram (QS morphology) from the earliest site. The local intracardiac electrograms at the same site before the start of successful ablation are shown. (B) Biventricular isopotential map (yellow color denotes the earliest activation) during preexcitation from a right posteroseptal accessory pathway (12-lead ECG) which was successfully ablated at the same site (local electrogram shown). Also inserted is a virtual electrogram (QS morphology) from the site of earliest ventricular activation over the manifest pathway. Abbreviations: Ao, aortic root; LAD, left anterior descending artery; LAO, left anterior oblique; MV, mitral valve; PA, pulmonary artery; TV, tricuspid valve.

to guide catheter ablation. The pre- and per-procedural utility of the system in panoramic 3D mapping expresses its potential to reduce invasive procedural, fluoroscopic and ablation times.

Disclosures Drs Haissaguerre, Hocini, Jais and Dubois are stockowners in CardioInsight Inc., Cleveland, OH, and Drs Shah and Dubois are paid consultants to CardioInsight Inc., Cleveland, OH. The other authors report no conflicts. Acknowledgment This work was supported through Investment of the Future GrantANR-10-IAHU-04 from the government of France through the Agence National de la Recherche.

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