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How to Utilize Noninvasive Guidance for Persistent Atrial Fibrillation

Ashok J. Shah, MD; Seigo Yamashita, MD; Mélèze Hocini, MD; Michel Haïssaguerre, MD; and Pierre Jaïs, MD

Introduction

Catheter ablation has evolved over last two decades into a mainstream therapy for atrial fibrillation (AF).^1–6 Emergence of data on 5- to 10-year follow-up after one or more ablation procedures has reinforced that persistent and longstanding persistent AF pose the biggest challenge to catheter-based therapy.^7–12 Analysis of these most complex clinical AF varieties using a noninvasive mapping technique has shown how localized reentrant and focal sources play a role in perpetuating this arrhythmia. Catheter ablation of these drivers has been reported to be effective. In this chapter, we describe new clinical insights obtained from noninvasive mapping of persistent AF to guide catheter ablation.

Recently, AF mapping using activation¹³ or phase-based¹⁴ analysis of body surface potentials has allowed potential visualization of AF-driving substrate in the form of multiple wavelets and reentrant drivers. Prior knowledge of key AF-driving regions has been shown to facilitate the ablation procedure in patients with persistent AF.¹⁴

Noninvasive Analysis of AF

Multiple atrial wavelets, macroreentries, and localized sources (focal or reentrant) have been reported to lead to maintenance of AF.^15–16 Electrical activities in the myocardium during AF can be mapped with electrode arrays in the in situ heart¹⁷ and voltage-sensitive fluorescent dyes in the isolated heart¹⁸ to demonstrate complex and often irregular activity. A study in human subjects involving epicardial mapping of induced AF demonstrated multiple dynamic wavefronts interacting with changing arcs of conduction block and slow conduction.¹⁹ Another study mapping chronic AF intraoperatively demonstrated short, regular cycle lengths that could be consistent with a driver with irregular activation of rest of the atrium.²⁰ Although it is now well accepted that the irregular waveform is related to an irregular and constantly changing activation sequence on the surface electrogram during AF, these drivers are difficult to detect in practice with conventional techniques because of continuous and intermittent spatiotemporal dynamicity of underlying sources.^21,22 To assess driver activity, phase analysis has been applied to these signals. Because of wavefront interactions leading to constant fractionation and collision, phase provides an amplitude-independent manner to characterize and visualize dynamic data.²³ Noninvasive mapping enables panoramic beat-to-beat mapping of this dynamic rhythm using phase analysis.^9,14

Noninvasive AF-Mapping Technique

Electrocardiographic imaging, which noninvasively images cardiac electrical activity in the heart, has been developed recently.^24–26 This novel modality can demonstrate reconstructed unipolar electrical potentials, electrograms, and isochrones on the epicardium by using geometric information from computed tomography (CT) and an inverse mathematical algorithm.²⁷ Based on the inverse principle, the clinical utility of noninvasive mapping in atrial and ventricular arrhythmias has been reported.^28–31 Mapping is undertaken by using commercially available system (ECVUETM, Cardioinsight Technologies, Cleveland, OH). After acquiring 64-section multi-detector CT images with a vest of 252 body-surface electrodes positioned on the thorax and upper abdomen, epicardial unipolar electrograms are reconstructed on a patient-specific biatrial geometry.²⁷ In persistent AF patients presenting in sinus rhythm, coronary sinus pacing is used to induce sustained AF (lasting > 10 minutes). Clinical or induced AF electrograms are acquired during a long ventricular pause, whether spontaneous or diltiazem-provoked. QRST is subtracted and AF maps are created using specific algorithms combining wavelet transform and phase mapping applied to the reconstructed epicardial potentials. Activation maps are computed using traditional unipolar electrogram intrinsic deflection-based (–dV/dT_max) method. The AF drivers can be classified into 2 categories: (1) focal activation with centrifugal propagation from a point, and (2) reentry/rotor demonstrating rotated wave with full phase propagation around a functional or anatomical center point. The core and trajectory of reentrant drivers and focal sources are depicted on the patient-specific biatrial geometry (Figure 15.1A–C).^28,32 The number of foci and reentry through the total duration of all AF-windows are displayed on cumulative driver-density maps.

Distribution and Characteristics of Localized AF Drivers

Noninvasive mapping reveals multiple locations of drivers in persistent AF. These drivers demonstrate abrupt appearance at single or multiple sites and reproducibly rotate few times, often showing meandering spatiotemporal motion. In our previous report,14 repetitive reentrant activities (> 1 rotation) were observed in 73% of reentrant drivers with median 2.6 (IQR 2.3–3.3) repetitive rotations. The trajectory of reentrant driver core was spread over mean 7 ± 2 cm²; accordingly, the map displays driver location not over a discrete site but over a certain area with variable density (Figure 15.1C). The drivers were located in pulmonary veins (PVs) and their respective antra in about 90% patients in paroxysmal AF, where approximately 50% of patients demonstrated non-PV foci and reentry.³³ In persistent AF, the left PV appendage (ridge), the right PV/septum, and the inferior left atrium (LA) were most common locations of the reentrant driver. The focal driver originated from PV ostium and right or left appendages with a median of four regions.¹⁴ The prevalence and distribution of drivers depend on the clinical duration of AF such that the total number of driver regions and activities increase with the length of continuous AF, indicating that the driver characteristics are associated with the extent of atrial remodeling. Previous report demonstrated that longstanding AF had a larger LA surface with a greater amount of total scar (delayed enhancement area on MRI) and more continuous complex fractionated atrial electrogram (CFAE) surface area than persistent AF.³⁴ The relationship between CFAE sites and localized drivers is not clear. In our study, prolonged fractionated electrograms were more frequently observed at the reentrant driver regions compared with non-driver regions (62% vs. 40%, P = 0.04). Additionally, electrograms recorded on a multielectrode catheter, although not simultaneously with noninvasive mapping, covered most of the AF cycle length at the driver regions, which indicate towards the possibility of localized reentry.¹⁴ Of note, 50% of CFAE sites have been reported to be passive bystanders due to nonlocal signal or wave collisions.^35,36 Noninvasive mapping may be considered to reveal critical CFAE sites harboring localized AF drivers. Interestingly, a previous report showed that 89% of CFAE sites were located at nonscar and patchy scar areas (41% at patchy fibrosis area, 48% at healthy area).³⁴ Another study demonstrated that localized reentrant drivers are located at the border of fibrotic areas,³⁷ with the good correlation between LA fibrosis burden and the number of localized reentrant driver regions (R = 0.42, P = 0.04). It suggested that border zone of fibrosis allows formation of a substrate favorable for slow conduction and reentry of wavelets (reentrant driver) capable of perpetuating AF.³⁷

Noninvasive Mapping-Guided Ablation

The order of ablation is determined based on the cumulative driver map (Figure 15.1C). After acquiring atrial geometry on 3D electroanatomic mapping system (CARTO 3, Biosense Webster, Inc., Diamond Bar, CA), the region having the highest density of reentrant drivers is targeted first, followed by the region with the second-highest driver density, and so on. The ability to terminate AF correlates with the duration of uninterrupted AF (Figure 15.2A) and with the number of driver regions (Figure 15.2B). Within the driver area, rapid and continuous fragmented signals and activation gradient between proximal and distal electrodes are locally mapped and targeted for ablation.³⁸ The endpoint of radiofrequency (RF) application is elimination of fragmented potentials and slowing of the AF cycle length at the local site (Figure 15.3). Each RF application targets dominant clusters of AF drivers at 30 to 40 W (25 W in posterior wall) using an irrigated-tip catheter with temperature cut-off set at an angle of 45°. If AF persists after ablation of the first targeted region, the second-highest-density area of drivers is subsequently ablated in the same way (Figure 15.3). The endpoint of the procedure is AF termination (sinus rhythm or atrial tachycardia) or completion of RF applications targeting all driver areas. If the drivers are found to be present around PVs, ipsilateral PV isolation is routinely performed. Reentrant drivers are more preferentially targeted than focal drivers because of the fact that sites harboring atrial focal activities during AF were not found to be strongly associated with AF termination.³⁷ Also, stable drivers with good-quality signals on noninvasive map are targeted regardless of their type. AF sustained after driver-based ablation is electrocardioverted.

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