Thursday, May 18, 2017

Ganglionic plexus ablation for atrial fibrillation: disappointing results

This paper in JACC introduces another category in the classification of atrial fibrillation: advanced AF. From the paper:

..advanced AF, defined as persistent AF, enlarged left atria, or previously failed catheter ablation.

The paper also reviews the indications and rationale for various types of ablation:

The arrhythmogenic trigger from the pulmonary veins (PVs) is the target for ablation in patients with paroxysmal AF without concomitant atrial or cardiac disease; the mechanism is less well established in patients with advanced AF, defined as persistent AF, enlarged left atria, or previously failed catheter ablation. Various treatment strategies have been advocated, combining more extensive myocardial ablation and ablation of non-PV and nonmyocardial targets, including stepwise catheter ablation approaches (3), in which PV isolation (PVI) is followed by linear left atrial (LA) ablation, ablation of continuous fractionated atrial electrograms (4), or ablation of rotors (5).

Furthermore, the rationale for ganglionic plexus (GP) ablation is explained:

As it has become clear that the autonomous nervous system plays a central role in initiating AF and in atrial autonomic remodeling (6,7), partial atrial denervation through ablation of the major autonomic ganglion plexus (GP), either alone or in combination with PVI, has been pursued (8,9).

GP stimulation promotes AF by a combined parasympathetic and sympathetic action resulting in action potential duration (APD) shortening and increased sarcoplasmic reticulum calcium release in PV myocardium, allowing early after-depolarizations to emerge and trigger AF (10). Aside from AF induction, GP stimulation affects local and global LA conduction time, consistent with a predominantly parasympathetic effect (11). Thus, the stimulation of the autonomic nerves within the GPs, beyond triggering AF, may also have a proarrhythmic effect on the atrial myocardium that perpetuates the arrhythmia (11).

Studies investigating the role of GP ablation in addition to PVI have demonstrated mixed results (8,12,13), as have nonrandomized studies during concomitant cardiac surgery (14,15).

This paper reports further results, which were disappointing:

Background Patients with long duration of atrial fibrillation (AF), enlarged atria, or failed catheter ablation have advanced AF and may require more extensive treatment than pulmonary vein isolation.

Objectives The aim of this study was to investigate the efficacy and safety of additional ganglion plexus (GP) ablation in patients undergoing thoracoscopic AF surgery.

Methods Patients with paroxysmal AF underwent pulmonary vein isolation. Patients with persistent AF also received additional lines (Dallas lesion set). Patients were randomized 1:1 to additional epicardial ablation of the 4 major GPs and Marshall’s ligament (GP group) or no extra ablation (control) and followed every 3 months for 1 year. After a 3-month blanking period, all antiarrhythmic drugs were discontinued.

Results Two hundred forty patients with a mean AF duration of 5.7 ± 5.1 years (59% persistent) were included. Mean procedure times were 185 ± 54 min and 168 ± 54 min (p = 0.015) in the GP (n = 117) and control groups (n = 123), respectively. GP ablation abated 100% of evoked vagal responses; these responses remained in 87% of control subjects. Major bleeding occurred in 9 patients (all in the GP group; p less than 0.001); 8 patients were managed thoracoscopically, and 1 underwent sternotomy. Sinus node dysfunction occurred in 12 patients in the GP group and 4 control subjects (p = 0.038), and 6 pacemakers were implanted (all in the GP group; p = 0.013). After 1 year, 4 patients had died (all in the GP group, not procedure related; p = 0.055), and 9 were lost to follow-up. Freedom from AF recurrence in the GP and control groups was not statistically different whether patients had paroxysmal or persistent AF. At 1 year, 82% of patients were not taking antiarrhythmic drugs.

Conclusions GP ablation during thoracoscopic surgery for advanced AF has no detectable effect on AF recurrence but causes more major adverse events, major bleeding, sinus node dysfunction, and pacemaker implantation. (Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery [AFACT]; NCT01091389)

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