Atrial Conduction Slows Immediately Before the Onset of Human Atrial Fibrillation

Abstract

Objectives The aim of this study was to determine whether onset sites of human atrial fibrillation (AF) exhibit conduction slowing, reduced amplitude, and/or prolonged duration of signals (i.e., fractionation) immediately before AF onset. Background Few studies have identified functional determinants of AF initiation. Because conduction slowing is required for reentry, we hypothesized that AF from pulmonary vein triggers might initiate at sites exhibiting rate-dependent slowing in conduction velocity (CV restitution) or local slowing evidenced by signal fractionation. Methods In 28 patients with AF (left atrial size 43 ± 5 mm; n = 13 persistent) and 3 control subjects (no AF) at electrophysiological study, we measured bi-atrial conduction time (CT) electrogram fractionation at 64 or 128 electrodes with baskets in left (n = 17) or both (n = 14) atria during superior pulmonary vein pacing at cycle lengths (CL) accelerating from 500 ms (120 beats/min) to AF onset. Results Atrial fibrillation initiated in 19 of 28 AF patients and no control subjects. During rate acceleration, conduction slowed in 23 of 28 AF patients (vs. no control subjects, p = 0.01) at the site of AF initiation (15 of 19) or latest activated site (20 of 28). The CT lengthened from 79 ± 23 ms to 107 ± 39 ms (p < 0.001) on acceleration, in a spectrum from persistent AF (greatest slowing) to control subjects (least slowing; p < 0.05). Three patterns of CV restitution were observed: 1) broad (gradual CT prolongation, 37% patients); 2) steep (abrupt prolongation, at CL 266 ± 62 ms, 42%); and 3) flat (no prolongation, 21% AF patients, all control subjects). The AF initiation was more prevalent in patients with CV restitution (17 of 23 vs. 2 of 8; p = 0.03) and immediately followed abrupt reorientation of the activation vector in patients with broad but not steep CV restitution (p < 0.01). Patients with broad CV restitution had larger atria (p = 0.03) and were more likely to have persistent AF (p = 0.04). Notably, neither amplitude nor duration (fractionation) of the atrial signal at the AF initiation site were rate-dependent (both p = NS). Conclusions Acceleration-dependent slowing of atrial conduction (CV restitution) precedes AF initiation, whereas absence of CV restitution identifies inability to induce AF. Conduction restitution, but not fractionated electrograms, may thus track the functional milieu enabling AF initiation and has implications for guiding AF ablation and pharmacological therapy.

Human Atrial Fibrillation Initiates via Organized Rather Than Disorganized Mechanisms

“…These electrograms are typically discrete, without fractionation, allowing construction of unambiguous isochronal maps. Activation time at each electrode was defined as the point of steepest slope of the first negative deflection in software 11 using filtering 12 , then manually over-read blinded to the spatial map (Fig. 1c.…”

Human Persistent Atrial Fibrillation Is Maintained by Rotors

“…Rappel and Narayan 22 have acknowledged that no mapping technique can resolve spatial events with a length scale smaller than the interelectrode spacing, and that noise in electrogram recordings will affect the resolution of basket catheter mapping. They have argued that wavelength considerations rooted in human atrial electrophysiology indicate a minimum spiral wavelength of 4 to 5 cm [23][24][25] and have reported FIRM mapping to provide a spatial resolution of <10 mm 15 and a temporal resolution of 1 ms. 22 In this study by Benharash et al 21 and in others using FIRM mapping, 26 the lack of distinguishing electrogram features at the putative site of focal drivers such as rotors is a striking finding. Electrograms at FIRM-identified ablation sites were not found to differ in dominant frequency or Shannon entropy values compared with the atrial regions that did not harbor focal AF drivers.…”

Independent mapping methods reveal rotational activation near pulmonary veins where atrial fibrillation terminates before pulmonary vein isolation

“…Briefly, unipolar AF signals (0.05-500 Hz) were recorded using basket catheters, deactivating the localization signal of the electroanatomic mapping system to minimize electronic noise. Electrograms were analyzed using algorithms to filter far-field using monophasic potential data to estimate repolarization 15 and conduction 16,17 and create activation maps (grayscale).…”