Human atrial fibrillation initiates via organized rather than disorganized mechanisms

Abstract

Background: It is unknown how atrial fibrillation (AF) is actually initiated by triggers. Based on consistencies in atrial structure and function in individual patients between episodes of AF, we hypothesized that human AF initiates when triggers interact with deterministic properties of the atria and may engage organized mechanisms.

Methods and results: In 31 patients with AF, we mapped AF initiation after spontaneous triggers or programmed stimulation. We used 64-pole basket catheters to measure regional dynamic conduction slowing and to create biatrial activation maps during transitions to AF. Sixty-two AF initiations were recorded (spontaneous, n=28; induced, n=34). Notably, AF did not initiate by disorganized mechanisms, but by either a dominant reentrant spiral wave (76%) or a repetitive focal driver. Both mechanisms were located 21±17 mm from their triggers. AF-initiating spirals formed at the site showing the greatest rate-dependent slowing in each patient. Accordingly, in 10 of 12 patients with multiple observed AF episodes, AF initiated using spatially conserved mechanisms despite diverse triggers.

Conclusions: Human AF initiates from triggers by organized rather than disorganized mechanisms, either via spiral wave re-entry at sites of dynamic conduction slowing or via repetitive focal drivers. The finding that diverse triggers initiate AF at predictable, spatially conserved functional sites in each individual provides a novel deterministic paradigm for AF with therapeutic implications.

Keywords: arrhythmias, cardiac; atrial fibrillation; cardiac electrophysiology; spiral waves.

Conflict of interest statement

Conflict of Interest Disclosures: Drs. Narayan and Rappel are authors of intellectual property owned by the University of California Regents and licensed to Topera Inc. Topera does not sponsor any research, including that presented here. Drs. Narayan and Rappel hold equity in Topera. Dr. Narayan reports having received honoraria from Medtronic, St. Jude Medical, and Biotronik. Drs. Schricker, Lalani, and Krummen report no conflicts.

© 2014 American Heart Association, Inc.

Figures

Figure 1

Catheter placement and recordings of AF initiation. (a) Fluoroscopy showing 64-pole basket catheter in each atrium, implanted ECG monitor (Reveal, Medtronic, MN), catheters in the coronary sinus and LA, and esophageal temperature probe. (b) ECG and intracardiac signals of spontaneous paroxysmal AF after a PAC trigger, with (c) activation time marking of electrogram. (d) NavX shells of both atria indicating the trigger and region of interest, with separation computed from respective (x,y,z) coordinates. (IVC=inferior vena cava, LA=left atrium, MV=mitral valve, RA=right atrium, SVC=superior vena cava, TV=tricuspid valve.)

Figure 2

Bi-atrial spatial activation maps for a sinus beat and premature atrial complex (PAC) in a 74-year-old man with paroxysmal AF. (a) Sinus activity propagates centrifugally in the RA and conducts via Bachmann’s bundle to the LA. (b) Non-AF initiating PAC from the lateral LA shows non-centrifugal activation in the RA, with preferential septal-to-lateral slowing (zig-zag line). (c) Corresponding intracardiac recordings.

Figure 3

Multiple AF initiations via a spiral wave in an 81-year-old man with paroxysmal AF. (a) Spontaneous initiation: ECG and intracardiac recordings. Electrograms 1–12 represent sites 1–12 in panel (b). (b) Spatial activation maps show the corresponding sinus beat (top panel) followed by a spontaneous RA PAC (middle panel, red star, >22ms earlier than other sites) causing slowed conduction in the inferior RA. The first AF cycle (bottom panel) encounters tissue that activated late in the prior beat, causing block with formation of a counterclockwise spiral wave in the mid-septal RA that initiates AF. (c) Pacing-induced AF initiation, 10 minutes after the previous initiation, at burst pacing CL260ms near the right superior PV. Electrograms 1–11 represent sites 1–11 in panel (d). (d) Steady-state pacing (top panel, electrograms not shown) shows rapid activation that slowed with increasing rate in RA as shown in the final 2 paced beats prior to AF (second and third panels, respectively) leading to an AF-initiating spiral with similar location and CL to panels (a, b). Color maps in (d) represent true RA activation time referenced to pacing artifact. Despite different LA activity and quite different triggers, the same AF-initiating RA spiral wave is formed. Black areas represent diastole in the transition to established AF.

Figure 4

Multiple AF initiations via a repetitive focal driver in a 67-year-old man with persistent AF. (a) ECG and intracardiac recordings and (b) bi-atrial spatial activation map showing the last sinus beat (top panel), followed by a LA PAC trigger (middle), which leads to a focal AF driver on the anterior LA (CL150ms; bottom). (c) Left atrial activation map from 4 additional spontaneous initiations, each initiated by spatiotemporally similar focal drivers despite various preceding triggers.

Figure 5

AF initiation by a right atrial spiral wave at the site of dynamic conduction slowing. (a) RA activation map during LA pacing at baseline (CL450ms), intermediate (CL360ms), and rapid (CL200ms) rates, corresponding to sites (i, ii, iii) on the (b) conduction restitution curve, illustrating rate-dependent conduction slowing in the low posterior RA (black square). Critical delay in activation in the low RA at the fastest rate (pre-fibrillatory slowing, red line) causes block and (c) forms a counterclockwise spiral that initiates AF. (d) Corresponding ECG and intracardiac recordings.

Figure 6

Conserved initiation of AF in 10 patients with multiple initiations. Right and left atria displayed for each patient with the location of the conserved initiating mechanism and triggers for each individual initiation. Section headings display the number of conserved initiations engaging the common initiating mechanism. Numbers in parentheses indicate multiple triggers from that location. Triggers depicted outside both atria represent an inter-atrial septum origin