The Autonomic Nervous System and Atrial Fibrillation:The Roles of Pulmonary Vein Isolation and Ganglionated Plexi Ablation

Abstract

After the sequential successes of catheter ablation for the treatment of pre-excitation syndromes (WPW), junctional reentry (AVNRT) atrial flutter (AFL) and ventricular arrhythmias, clinical electrophysiologists have focused on the myocardial basis of atrial fibrillation (AF). Thus, the strategy for ablation of drug and cardioversion refractory AF was to isolate the myocardial connections from the focal firing pulmonary veins (PVs) in addition to altering the atrial substrate maintaining AF. However, the overall success rates have not achieved those of the other types of ablation procedures. In this review we have summarized the favorable aspects and drawbacks of pulmonary vein isolation (PVI). As for the role of the Intrinsic Cardiac Autonomic Nervous System (ICANS), both basic and clinical evidence has shown that ganglionated plexi (GP) stimulation promotes initiation and maintenance of AF, and that GP ablation reduces recurrence of AF following catheter or surgical ablation of these structures. Based on these findings, the GP Hyperactivity Hypothesis has been proposed to explain, at least in part, the mechanistic basis for the focal form of AF. For example, PV isolation may not always be necessary for elimination of AF, as in the early stages of paroxysmal AF. GP ablation alone, in these cases, may suffice for focal AF termination. In the persistent and long standing persistent forms the substrate for AF may be more extensive and therefore require GP ablation plus PV isolation and/or CFAE ablations. Clinical reports, both catheter based as well as minimally invasive surgical procedures, which include PVI plus GP ablation have shown relatively long-term success rates much closer to or equal to those achieved by myocardial ablation procedures in patients with WPW, AVNRT and AFL.

Figure 1.. A diagrammatic representation of the neural network that extends over the right and left atria as well as on the epicardial surface of the ventricles. This illustration is the drawing taken from the publication by Pauza et al. showing the course of nerves which were seen after acetycholinesterase staining. In this study, ganglia within fat pads are not depicted although as many as 4300 intrinsic neurons were estimated to be found in the adult human heart. (Reproduced by permission from Pauza et al. Anatomic Record 2000;259:353-382.)

Figure 2.. View of the fat pads (panel A) on the human heart as seen through a right thorascopic port. The fat pads (which contain the anterior and inferior right GP) are shown within the demarcated areas (dashed lines) lying between the right superior and right inferior pulmonary veins (RSPV, RIPV). Panel B. A thorascopic view from a left sided port showing the left superior and left inferior, LSPV, LIPV as well as the ligament of Marshall (LOM). The superior left GP is located at the junction of the LSPV and the pulmonary artery while the left inferior GP is located inferior and posterior to the LIPV

Figure 3.. CARTO map showing the localization of the GP adjacent to the 4 PVs by high frequency stimulation (HFS) from an electrode catheter placed endocardially subjacent to each of the epicardial fat pads containing the GP. Note that the encircled red dots indicate the sites at which a marked slowing of the ventricular rate was observed during HFS applied at that site (see [Figure 4])

Figure 4.. A typical response to HFS at a GP site during ongoing AF which consists of a marked slowing of the ventricular response due to an initial strong parasympathetic effect causing suppression of A-V conduction for about 3 seconds. With termination of GP stimulation the ventricular rate is quickly restored

Figure 5.. The effect of locally applied acetylcholine (ACH) on the conversion of a Type I electrogram to one showing various forms of fractionation, i.e., complex fractionated atrial electrogram, (CFAE). Traces include ECG lead II, His bundle recording (HB), bipolar electrograms from the right (R) and left (L) atrial (A) free walls, R and L pulmonary veins (PVs) and right atrial appendage (RAA). Panel A. The trace labeled RAp represents a bipole on an electrode catheter which showed a Type I electrogram during AF (no CFAE). It was chosen to be locally painted with various concentrations of Ach. Panel B. There was no change when Ach, 1mM was applied to this bipole (no CFAE). Panel C. However, when 10mM Ach was applied to this site intermittent CFAE was noted. Panel D. The subsequent local application of 100mM Ach resulted in the appearance of continuous CFAE. See text for further discussion. (Reproduced with permission from Lin et al J Cardiovasc Electrophysiol 2007;18:1197-1205)