Ablation of Atrial Fibrillation Drivers: Focal Impulse and Rotor Modulation

Introduction

Approaches for the ablation of atrial fibrillation (AF) have changed rapidly in the past two decades and are focused on eliminating triggers near and from the pulmonary veins (PVs), which may initiate AF. PV-guided ablation ameliorates AF in many patients , yet success remains suboptimal even in recent studies using force sensing catheters or cryoballoon ablation to minimize PV reconnection. Adding extensive ablation of complex fractionated electrograms or linear lesions have not improved the results of PV isolation (PVI) in recent multicenter trials.

Focal and rotational drivers for AF are increasingly studied ablation targets, whose mechanistic role has long been defined in translational studies and for which there is steadily increasing evidence in patients. Focal impulse and rotor mapping (FIRM), the most widely applied method to map AF drivers, reveals focal and rotational drivers, which may spatially overlap drivers in recent optical mapping studies of human AF and are similar to AF drivers described by other methods. Several important clinical questions currently exist. First, despite promising overall outcomes of AF driver ablation in a metaanalysis, it is unexplained why outcomes vary between centers. Second, there is a lack of practical guidance on how to optimally map and ablate AF drivers and avoid pitfalls. Third, it is unclear if different AF mapping methods would show similar or different features in the same patient. This chapter provides a practical clinical overview that attempts to address these topics.

Mechanistic Targets for Therapy: Rotational Drivers, Focal Drivers, and Disorganization

Despite decades of pharmacologic, surgical, and ablative therapy for AF, gaps in our mechanistic understanding of AF greatly limit ablation efficacy. Early mechanistic models suggested that AF was caused by the asynchronous discharge of numerous ectopic foci, but more recent studies have supported reentrant mechanisms. Fig. 18.1A shows classical reentry around an anatomic obstacle, with a fully excitable gap between leading and trailing edges ( head and tail ). In the leading circle hypothesis, functional reentry is maintained by a wave front encircling an area of tissue that remains refractory from constant centripetal activation, which in turn stabilizes the circuit ( Fig. 18.1B ). Disorganized models of AF have invoked either intermittent foci or meandering leading circle reentry, which suggests the need for extensive ablation to treat AF and largely reduce the importance of mapping.

Spiral wave reentry was first proposed in computer models, then revealed using optical mapping in isolated fibrillating ventricular muscle ( Fig. 18.1C ). A spiral wave rotates around a core in 2 dimensions, and a scroll wave rotates around a “filament” in 3 dimensions ( Fig. 18.1D ), each of which has a shorter path length than the periphery ( Fig. 18.1E ). At the core, the wave front (solid line in Fig. 18.1E ) encroaches upon the wave tail (dotted line), resulting in less depolarizing current, and slowed conduction velocity (arrows). Conduction slowing enables reentry near the core, where meeting of the wave front/tail meet reduce conduction velocities towards zero ( white asterisk , see Fig. 18.1C ). The core is thus unexcited yet potentially excitable. This differs fundamentally from leading circle reentry in which the center is excited and unexcitable. Fig. 18.1F depicts a snapshot of a computer-generated spiral wave. The spiral wave core and surrounding functional reentry form a “rotor.” This concept provides organizing centers for AF, whether one or multiple, which may in theory be ablation targets.

There is now considerable direct evidence that rotors sustain fibrillation, using optical mapping in isolated hearts from multiple species including human AF. Optical mapping ( Fig. 18.2 ) uses video imaging of voltage-sensitive dye imaging, coupled with phase, activation, or other signal-processing approach, to produce high spatial and temporal resolution maps of AF. Fig. 18.2A illustrates rapid irregular action potentials at one point mapped optically. Fig. 18.2B plots such action potentials across the cardiac surface in fibrillation. Each color represents phase (from activation to repolarization) such that rotations can be traced through the color spectrum (from red to blue). Points in the atrium where activation and repolarization meet, that is, around which an entire cycle can be traced, have undefined phase and are termed phase singularities (PS), which may represent rotor cores. Rotors are not fixed like reentry around an obstacle but may precess in limited areas with complex trajectories ( Fig. 18.2C ). Fibrillation may thus terminate when the rotor collides with a boundary, does not have enough elbow room to spin, or via other mechanisms.

Rotors were not consistently shown during clinical AF ablation until recent advances in mapping. Nevertheless, early work by Schuessler, Cox, and colleagues revealed stable reentrant sources that Maze surgery was designed in part to interrupt. Moreover, localized sources for AF have long been supported by observations including termination of persistent AF by localized ablation, detection of localized high dominant frequency suggesting rapid drivers, and spatially consistent activation vectors in AF that contradict disordered waves.

Historically, it was considered that AF resulted from the multi-wavelet and related models, which posit that disorganized activity generates new wavelets. This model requires no driver region per se , and hence that AF can be eliminated only by limiting critical mass, for example, extensive ablation or surgery. However, extensive ablation that limits atrial mass did not improve the elimination of AF in recent clinical trials, and the disorganized AF model does not readily explain the now routine termination of persistent AF by targeting identified regions in multiple studies in at least some patients. Work is needed to better reconcile the source and disorganized models of AF.

The terms spiral wave and rotor are often used interchangeably in the context of cardiac arrhythmias, yet nomenclature in this field is highly controversial. The term rotor is typically applied to the singular spatial point of rapid rotational activity, while spiral waves refers to the curvilinear emanating wave fronts of activation. Clinically the terms rotational activity, rotational driver, or even reentry are equally effective to describe the phenomena now mapped by multiple approaches.

Rationale for Mapping Human Atrial Fibrillation: Applying Basic Science to Patients

The mechanistic debate in AF has been amplified because it has only recently been appreciated that different mapping methods yield different mechanisms. This is not true for organized rhythms (e.g., atrial flutter), and which most systems basically agree. One specific difficulty with fibrillatory waves is that an electrode antenna may capture several local and far-field waves. There are few means of separation except knowledge, which falls within the refractory period, yet whose inclusion or exclusion may dramatically alter perceived mechanisms. Another difficulty is that temporospatial activity changes rapidly within AF, which challenges mapping.

Our laboratory commenced studies of human AF in the early 2000s using monophasic action potentials (MAPs) to reveal repolarization and multipolar catheters to measure conduction velocity in human atria during pacing and AF, and targeted ablation. It became clear in early studies that unipolar, bipolar, and MAP signals in AF differ dramatically, with examples of signals that appeared local in bipolar recordings actually being far field–that is, they lay within repolarization indicated uniquely by the MAP. This may explain why optical maps of AF, which are based on local action potentials, generally show rotational drivers of AF, whereas traditional AF activation maps show only disordered activity.

We set out to physiologically approximate optical maps in the electrophysiology laboratory, using signal processing to exclude far-field based on repolarization data from MAPs, followed by analyses of conduction velocity, and by validation of mechanisms by patient-specific targeted ablation. This led to focal impulse and rotor mapping/modulation (FIRM).