Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with an increased risk of morbidity and mortality. A subanalysis of the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) suggests that there is a significant survival benefit in the maintenance of sinus rhythm (SR), if it can be achieved without the potential adverse effects associated with antiarrhythmic drugs.1 The limitations associated with traditional AF therapies have fostered an interest in developing effective ablation strategies.
Over the past decade, catheter ablation has emerged as a potential cure for paroxysmal AF (PAF) and chronic AF (CAF). Currently, the two main strategies used for all AF ablation are pulmonary vein antrum isolation (PVAI)2 and circumferential pulmonary vein ablation (CPVA).3 In this article, the question of which of these two strategies is a better initial step for ablation of persistent and permanent forms of AF will be discussed, and the continuing evolution of adjuvant strategies in the quest to eradicate CAF will be explored.
Treatment Strategies for Chronic Atrial Fibrillation Ablation
Is Complete Pulmonary Vein Isolation Necessary?
Haissaguerre and colleagues reported that in 95% of AF patients, focal discharges were responsible for the initiation of AF originating in at least one PV sleeve.4–6 More recent studies suggest that the PVs play a role in the maintenance of AF.7–9 Strategies that electrically disconnect the PVs incarcerate these triggers, thus preventing their interaction with the atrial substrate and resulting in the conversion or termination of AF.
CPVA is reported to be effective in both PAF and CAF. The approach used for both PAF and CAF is the same. CPVA consists of creating a 3D reconstruction of the left atrium (LA), then widely encircling the PVs 1–2cm from their ostia. Additional linear lesions are placed at the posterior LA, roof, and mitral isthmus. This strategy assumes that the atrial tissue adjacent to the PVs is involved in the perpetuation of AF. CPVA is effective in 74% of patients with CAF at one-year follow-up (off antiarrhythmic drugs).10 While these success rates may appear relatively impressive, the real concern is that anatomically guided CPVA results in apparently coalescent but electrically incomplete lesions with residual conduction in 45–60% of the PVs, as shown by data from both our institution and Hocini and colleagues.11,12 Furthermore, at follow-up 20–24% of patients developed left atrial flutter.
PV isolation (PVI) is an effective treatment for most cases of PAF. The strategy used for PVI is identical in both PAF and CAF. Complete electrical PVI is the desired end-point, and is evidenced by the disappearance (entrance block) or dissociation (exit block) of PV potentials. This strategy assumes that the arrhythmogenic activity responsible for AF is confined within the PVs. However, despite isolation of the major trigger sources, 15% of patients with permanent AF and structural heart disease have further episodes of AF after multiple procedures, thus suggesting that there is a component in addition to PV focal discharges acting as the driver for AF in these CAF patients.13 Nevertheless, Haissaguerre and colleagues have shown that in cases of long-lasting persistent AF, PVs are one of three target ablation sites (coronary sinus and left atrial appendage being the other two) that have the greatest impact on the prolongation of AF cycle length, the conversion of AF to atrial tachycardia (AT), and the termination of focal ATs.14 Therefore, while solely isolating the PVs is certainly a ‘too minimal’ strategy for the treatment of CAF, it is still a necessary component of AF ablation in this subset of patients.
Over the past decade, this technique has evolved from focal PV ablation to PV ostial, and then to PVAI.15 The focus of AF ablation strategy has been to eliminate potential triggers of AF with additional substrate modification if necessary. At the Center for Atrial Fibrillation, PVAI is performed with the guidance of a circular mapping catheter and intra-cardiac echocardiography (ICE). Radiofrequency (RF) energy is delivered, targeting potentials on the portion of the circular mapping catheter that defines the PV antrum junction. In a stepwise fashion, the circular mapping catheter is moved to different locations along the PV antrum–LA junction, and further RF energy is applied until the entire PV antrum–LA junction is ablated and electrically isolated. Each ablation treatment has the end-point of local potential elimination; thus, the duration of energy application is not fixed and is dependent on the potentials being ablated. Further RF energy is applied to the posterior wall and the roof of the LA. The ablation of the roof should connect the superior portions of the left and right PV antrum (see Figure 1).12
Currently, the best imaging modality for defining the PV antra is either computed tomography (CT) or magnetic resonance imaging (MRI). However, these two modalities are limited because they are unable to generate realtime images. ICE can be used to precisely identify the true borders of the PV antrum, to provide realtime information on catheter location along the PV antrum–LA junction, to avoid complications, and to allow for optimal power delivery by using microbubbles as a gauge to guide energy titration. Such an approach gives a better chance of achieving transmural lesions.16
Non-pulmonary Vein Adjunctive Strategies
In patients with persistent or chronic long-standing AF and left atrial scarring, ablation of non-PV triggers and/or modification of the so-called atrial substrate may be required, prompting the evolution of adjunctive therapies. Non-PV adjunctive strategies that have emerged are septal ablation, ablation of other thoracic veins, ganglionic plexi, continuous fractionated atrial electrograms (CFAE), ‘AF nests,’ and atrial triggers.
It has been demonstrated that extending the ablation line from the anterior portion of the right PV antrum into the interatrial septum is associated with better clinical success rates in patients with CAF.17 It was also shown that isolation of the superior vena cava (SVC) is important.18
Ganglionic plexi—located at the PV antrum borders—could contribute to the initiation and maintenance of AF.19 In a study performed at the author’s institution, PVAI appears to be sufficient to target these plexi regions.20
Nademanee and colleagues have suggested that CFAE should be targeted for successful catheter ablation.21 CFAE areas may represent a substrate for AF perpetuation based on a demonstration of regional and temporal heterogeneity of endocardial atrial activation. Experience at the author’s center, and that of Haissaguerre’s group, shows that adjunctive CFAE ablation was associated with a higher incidence of intra-procedural rhythm conversion into AT.22 This acute end-point appears to correlate with higher long-term clinical success.
Realtime spectral mapping using fast Fourier transformations in SR localizes atrial regions called AF nests. Nests are identified by local bipolar electrograms that contain unusually high-frequency components.23 AF nests are commonly located at the base of the LA appendage, posterolateral mitral annulus, anterior aspect of the left interatrial septum, coronary sinus, low crista terminalis, and septal aspect of the SVC–right atrial junction. Ablation of these AF nests sites eliminates the high-frequency potentials and normalizes the spectrum of the local bipolar electrogram. Preliminary data from a prospective study evaluating the efficacy of AF nest ablation demonstrated a significant improvement in clinical success rates during short-term follow-up.24
For the past decade, the author’s group and the University of Pennsylvania group have used high-dose isoproterenol for initiation of atrial arrhythmias that may act as triggers for AF. Only sustained AT, or frequent premature atrial complexes that induce AF, are targeted.25
The end-point of this extensive ablation strategy for CAF is complete electrical isolation and elimination of any non-PV triggers that may contribute to AF. With this approach to permanent and persistent AF, a 90–91% success rate is achieved in the two procedures. A lower success rate is seen in patients with a left atrial scar, which is seen in 15–20% of permanent AF patients. In these cases, there are multiple extra antral foci, and a drug-free cure remains difficult to establish.10 However, with the incorporation of adjunctive strategies, cure is more likely (see Figure 2).
Nevertheless, catheter ablation for CAF is a complex procedure that is associated with significant risks. Previously, it was demonstrated that the antrum approach does not affect LA contraction.26 Whether the extensive ablation required to convert chronic AF into AT or SR has a detrimental impact on left atrial mechanical function needs to be assessed.
Recently, Haissaguerre and colleagues reported a stepwise ablation approach for CAF. They recommend that:
- PVI be guided and confirmed by a circular mapping catheter;
- linear ablation be performed at the LA roof between the left and right upper PVs;
- ablation of the inferior LA and coronary sinus, and LA ablation at any atrial site that exhibits continuous electrical and complex fractionated activity, and any focal site that appears to be a driver for AF;
- mitral isthmus ablation (if necessary); and
- optional right atrial/SVC ablation.
This stepwise approach suggests that targeting certain key structures in combination has a more synergistic effect on shortening atrial cycle length than if they were independently targeted. With this strategy, an excellent CAF conversion rate into either SR or AT of 87% is reported.27
Our group recently compared the acute and chronic outcomes of three different strategies for permanent long-standing AF. CPVA, PVAI, and CFAE and PVAI were compared. With a single procedure, SR was achieved in 11% of the patients in the CPVA group, 42% of the patients in the PVAI group, and 61% of the patients in the CFAE and PVAI group. After a repeat procedure, SR was maintained in 28% of the patients in the CPVA group, 83% of patients in the PVAI group, and 94% of the patients in the CFAE and PVAI group. This study suggested that a hybrid approach (CFAE and PVAI) has the best outcome after a single procedure.28 However, larger studies are necessary.
Finding the ideal strategy for CAF ablation is still an ongoing quest. Ablation of CAF is a complex and challenging procedure. More extensive procedures that target all possible sources of AF tend to be associated with better success rates. Unfortunately, more extensive procedures carry an increased risk of complications. Therefore, a strategy that reduces the amount of ablation is more desirable. However, at present the minimal lesion set required for termination of AF has yet to be determined. In the experience of the authors, isolation of all four PV antra is paramount to all types of AF ablation strategies. Currently, the strongest predictor for failure after PVAI is left atrial scarring. In such groups, a strategy that targets all additional non-PV triggers and or modifies the substrate may be the only chance of achieving a cure.