Atrial Substrate and Triggers of Paroxysmal Atrial Fibrillation in Patients With Obstructive Sleep Apnea

Abstract

Background: Obstructive sleep apnea (OSA) is associated with atrial remodeling, atrial fibrillation (AF), and increased incidence of arrhythmia recurrence after pulmonary vein (PV) isolation. We aimed to characterize the atrial substrate, including AF triggers in patients with paroxysmal AF and OSA.

Methods and results: In 86 patients with paroxysmal AF (43 with ≥moderate OSA [apnea-hypopnea index ≥15] and 43 without OSA [apnea-hypopnea index <5]), right atrial and left atrial voltage distribution, conduction velocities, and electrogram characteristics were analyzed during atrial pacing. AF triggers were examined before and after PV isolation and targeted for ablation. Patients with OSA had lower atrial voltage amplitude (right atrial, P=0.0005; left atrial, P=0.0001), slower conduction velocities (right atrial, P=0.02; left atrial, P=0.0002), and higher prevalence of electrogram fractionation (P=0.0001). The areas of atrial abnormality were consistent among patients, most commonly involving the left atrial septum (32/43; 74.4%). At baseline, the PVs were the most frequent triggers for AF in both groups; however, after PV isolation patients with OSA had increased incidence of additional extra-PV triggers (41.8% versus 11.6%; P=0.003). The 1-year arrhythmia-free survival was similar between patients with and without OSA (83.7% and 81.4%, respectively; P=0.59). In comparison, control patients with paroxysmal AF and OSA who underwent PV isolation alone without ablation on extra-PV triggers had increased risk of arrhythmia recurrence (83.7% versus 64.0%; P=0.003).

Conclusions: OSA is associated with structural and functional atrial remodeling and increased incidence of extra-PV triggers. Elimination of these triggers resulted in improved arrhythmia-free survival.

Keywords: atrial fibrillation; atrial remodeling; catheter ablation; incidence; prevalence.

Figure 1. Identification of AF Triggers

Panel A, isoproterenol infusion (20μg/min) did not induce atrial fibrillation (AF). However, the concomitant administration of adenosine bolus (48mg) resulted in increased AV block and initiation of AF (arrowhead). Panel B shows initiation of AF from a left atrial premature depolarization (APD). In this case, the initial induction of AF appeared to originate from the inter-atrial septum. Following restoration of sinus rhythm and preparation for a second induction of AF, the catheters were repositioned on the right (RA Sep) and left (LA Sep) inter-atrial septum. Note that during sinus rhythm, activation of the right septum (dotted line) precedes activation of the left septum (dashed line). The sinus beat is then followed by an APD-initiating AF originating from the left septum. Note the reversal of atrial activation with the left septum (dashed line) now preceding the right septum (dotted line).

Figure 2. Voltage and Conduction Properties in Non-OSA

The left panel shows a bipolar voltage map (range 0.1–0.5mV) of the right atrium (RA) in postero-anterior (top) and left anterior oblique (bottom) projections during proximal coronary sinus pacing in a patient without OSA. The voltage amplitude is normal. Activation map is presented as isochronal steps of 10ms, demonstrating early activation at the proximal coronary sinus pacing site with smooth and even propagation toward the zone of latest activation at the superior vena cava. The right panel shows bipolar voltage and activation maps of the left atrium at the left lateral (top) and right anterior oblique (bottom) projections during distal coronary sinus pacing. The voltage amplitude is normal (albeit the zone of the fossa ovalis) with normal wavefront propagation from the lateral mitral annulus to the zone of latest activation at the right superior pulmonary vein.

Figure 3. Voltage and Conduction Properties in OSA

The left panel shows bipolar voltage map (range 0.1–0.5mV) of the right atrium (RA) in postero-anterior (top) and left anterior oblique (bottom) projections during proximal coronary sinus pacing in a patient with OSA. This demonstrates an overall normal voltage amplitude, with small areas of lower voltage in the septum. The activation map, similarly presented as isochronal steps of 10ms, demonstrates slow and abnormal conduction in the septum with the mid-posterior septum being activated 258ms after the earliest activation of the proximal coronary sinus. The right panel shows bipolar voltage and activation maps of the left atrium at the left lateral (top) and right anterior oblique (bottom) projections during distal coronary sinus pacing. The voltage amplitude is abnormal with significant area of low voltage at the septum. The activation map during distal coronary sinus is abnormal, with slow conduction over the septum, at the zone of low voltage.

Figure 4. Bi-atrial Voltage and Conduction Abnormalities in OSA

The left panel shows voltage map (0.1–0.5mV) of the right and left atria from a patient with OSA. Note that the areas of low bipolar voltage primarily involve the inter-atrial septum. The middle panel shows electrogram recorded on the right inter-atrial septum during proximal coronary sinus pacing (CS 9–10) while the right panel shows electrograms recorded on the left inter-atrial septum during distal coronary sinus pacing (CS 1–2). Electrograms were recorded using a pentaray multi-electrode mapping catheter and demonstrates abnormal low and fractionated signals.

Figure 5

Distribution of AF Triggers in Patients with and without OSA

Figure 6. Stabilization of Electrical Activity around Zones of Low Voltage

In this example of a patient with OSA, a pentaray multielectrode mapping catheter was used to map the left atrium during atrial fibrillation (AF). A relatively stable beat-to-beat electrical activity was recoded around the zone of low voltage over the septum. Ablation at this location resulted in termination of AF.

Figure 7. Kaplan-Meier Survival Curves According to Treatment Groups

OSA, obstructive sleep apnea; PVI, pulmonary vein isolation