Ablation of Nonpulmonary Vein Triggers

Incidence of Nonpulmonary Vein Triggers

Most ectopic beats that trigger paroxysmal atrial fibrillation (AF) originate from pulmonary veins (PVs); therefore PV isolation (PVI) is an established procedure. However, recurrences without reconnection of PV have also been noted; thus many studies have demonstrated the importance of non-PV foci. Non-PV “triggers” can be identified in 10% to 33% of unselected patients referred for catheter ablation of AF. The prevalence of non-PV triggers in different studies varies with the specific definition adopted, which ranges from repetitive atrial premature depolarizations without definitive AF initiation to reproducibly triggering sustained AF. The incidence of non-PV foci is higher in patients with persistent AF and coexisting medical conditions, including chronic lung disease, than in those with paroxysmal AF. During redo ablation, non-PV triggers can be identified in nearly half of the patients. Non-PV triggers can be provoked in patients with both paroxysmal and more persistent forms of AF. In selected patients with reproducible non-PV triggers and without provocative PV triggers receiving high-dose isoproterenol (5–20 μg per minute), elimination of only the non-PV triggers has resulted in elimination of AF. Supraventricular tachycardias, such as atrioventricular (AV) nodal reentry or accessory pathway–mediated AV reciprocating tachycardia, can also be identified in up to 4% of unselected patients referred for AF ablation and can serve as a triggering mechanism for AF.

Origins of Nonpulmonary Vein Triggers

Mapping studies of non-PV foci have demonstrated that triggers are typically clustered in discrete anatomic regions that have been shown to contain cardiomyocytes that can exhibit arrhythmogenic activity. The superior vena cava (SVC) contains an atrial muscle extension from the embryonic sinus venous tissue capable of spontaneous ectopic activity and has been shown to be one of the most important sites of non-PV triggers. The posterior wall of the left atrium (LA) is known to be an extension of the PVs and becomes one of the important non-PV trigger foci. Diseased human atria show low diastolic potential and altered cellular responses compared with normal atria. This may account for abnormal automaticity or triggered activity arising from the posterior free wall of the LA. The ligament of Marshall (LOM) is a remnant of the left SVC that contains nerves, fibrous tissues, and muscle bundles (Marshall bundles) that directly connect to the atrial myocardium and coronary sinus (CS) muscle sleeves. Hwang et al. reported that this could be a potential source of triggers and drivers for AF, and catheter ablation of LOM is feasible and clinically useful. Myocardial fibers within the CS have also been reported to have triggered activity, which may serve either as a trigger for AF or as a part of a reentrant circuit. The crista terminalis (CT) is an area of marked anisotropy because of poor transverse cell-to-cell coupling, and such anisotropy, by creating a region of slow conduction, favors the development of macro- or microreentry. In addition, the normal sinus pacemaker complex is distributed along the long axis of the CT, which contributes to the automaticity. The interatrial septum, particularly at its muscular portion at the level of the fossa ovalis, has been reported to be another potential trigger site for AF. More recently, frequent and repetitive premature atrial depolarizations have been identified in the LA appendage (LAA) in patients with more persistent AF, which have been targeted by LAA isolation techniques.

Provocation and Mapping of Nonpulmonary Vein Triggers

Withholding of antiarrhythmic agents for five half-lives and withholding beta-blockers for at least 24 hours is important when a strategy of searching for non-PV triggers is used. A typical protocol for initiating non-PV triggers includes:

• 1.

  If the patient presents with AF, cardioversion is performed to restore sinus rhythm (SR) and check for spontaneous AF reinitiation with the specific aim of identifying postcardioversion AF triggers.

• 2.

  If the presenting rhythm is SR or if AF is not spontaneously reinduced after cardioversion, the following protocol is performed: (1) graded infusion of isoproterenol at up to 20 to 30 μg per minute for at least 10 minutes is recommended; (2) if no effect is observed with isoproterenol infusion, burst pacing for AF and then cardioversion during isoproterenol infusion (2–10 μg per minute) may be considered. Pacing for AF induction is performed using 15-beat drive train at an amplitude of 10 mA and a pulse width of 2 ms, decrementing by 10 ms from 250 to 180 ms or failure to capture with a 5-second pause between drives. Multiple cardioversions are typically necessary to see reproducibility of immediate reinitiation of AF postcardioversion.

• 3.

  Adenosine bolus (12–18 mg) or burst atrial pacing is used during lower-dose isoproterenol infusion to attempt to identify repetitive triggers after the drive train.

• 4.

  The end point of protocol to assess the effect of ablation for evaluating non-PV triggers is the inability to “trigger” AF with repeat isoproterenol or adenosine infusion.

The approach used to map non-PV triggers includes analysis of the initiating P wave morphology on the 12-lead electrocardiogram (ECG), analysis of the earliest endocardial site of activation at the multipolar CS and CT/SVC catheters referenced to the P wave onset, and detailed mapping of the origin outside the PVs by manipulating the circular mapping catheter and the ablation catheter ( Figs. 16.1–16.3 ) in the LA and right atrium (RA).

Potentials from both SVC and right superior PV (RSPV) can be recorded as far-field potentials rather than a local potential because the two structures are close in proximity. Thus the positioning of a catheter in SVC is obligatory when the trigger from a right-sided PV is evaluated.

After circumferential ablation of left-sided PVs, the potential recorded on multielectrode catheter inside each of the correspondent PVs should be evaluated to check whether PVs remain connected or LOM potential is exposed. The pacing maneuver in different sites (LAA and distal CS) is required to identify the presence of LOM potential. If the potentials are caused by connection through LOM between LA and CS epicardially, conduction delay can be observed in LAA pacing but not in distal CS pacing ( Figs. 16.4 and 16.5 ).

Catheters need to be moved to differentiate the site of interest. In case of non-PV triggers near the CS ostium, the catheters have to move into the septum of the RA and CS ostium to localize the trigger site. Every effort should be made to prevent mechanical ectopy by confirming stable catheter position and to avoid manipulating the catheters during induction of arrhythmias.

Ablation of Nonpulmonary Vein Triggers

Superior Vena Cava

The proximal SVC contains myocardium that connects to the RA, and thus atrial excitation or sinus node impulses can propagate into the SVC, and vice versa. SVC cardiomyocytes were found to have pacemaker activity, and the enhanced automaticity and after-depolarization play a role in the arrhythmogenic activity of SVC.

Typically, the P wave from the SVC will have a larger negative component in lead V1 than a right PV, which originates more posteriorly (see Fig. 16.1 ). The SVC can be divided into three parts. The first part extends from the junction of the right and left brachiocephalic veins to the upper end of the right pulmonary artery. The second part involves the SVC that is crossed posteriorly by the right pulmonary artery (i.e., from the upper border of the right pulmonary artery to the lower border of the right pulmonary artery). The third part begins from the lower end of the second part and extends to the site of the RA–SVC junction, which is defined as the point below which the cylindrical SVC flares into the RA ( Fig. 16.6 ). The SVC-RA junction can be confirmed using an SVC venogram, intracardiac echocardiography (ICE), and electrical signals. An SVC trigger displays the earliest activation from the muscular sleeve of the SVC, followed by distal to proximal SVC electrograms and atrial electrograms ( Fig. 16.7 ). A differential diagnosis between SVC triggers and triggers from nearby structures is challenging because of the close anatomic proximity between the SVC and other structures, such as the RSPV and the superior CT. In rare instances, a direct muscular connection between the RSPV and the SVC can be demonstrated with pacing maneuvers (i.e., intercaval bundle). In these cases, the distinction between a trigger from SVC and RSPV can be established only after RSPV isolation (with entrance and exit block) is accomplished.

For AF patients with an SVC trigger, electrical isolation of the SVC from the RA at the level of the RA–SVC junction is a preferable approach to avoid recurrence and SVC stenosis. The end point is the electrical conduction block from the RA to the SVC (entrance block). The exit block of the focal repetitive activity inside the SVC may be observed before and after ablation. A 3-dimensional mapping system can facilitate the electrical isolation of the SVC. The junction between the SVC and the RA can be easily imaged with ICE to guide positioning of the circular mapping catheter. When the circular mapping catheter is placed, radiofrequency (RF) energy should be applied just proximally to the circular mapping catheter. When delivering RF energy to the anterolateral SVC ostium, special caution is required. Increase in sinus node automaticity may be a warning sign of impending injury to the sinus node. It is crucial to pace the distal electrode of the ablation catheter at a high current level (minimum of 20 mA) to check the phrenic nerve stimulation before energy is delivered to the SVC or lateral RA wall to prevent phrenic nerve injury. It is also advisable to monitor the right hemidiaphragm fluoroscopically during ablation. In contrast to wide-area PVI, a segmental approach targeting the earliest breakthrough on the circular mapping catheter in the SVC is most commonly used.