Atrial fibrillation (AF) is the most common tachy-arrhythmia associated with significant morbidity. AF is well known as contributing to the development of stroke, with an estimated risk of 3–5% per year in untreated individuals.1 In addition, the results of the Framingham study showed a 1.5 to two-fold higher mortality rate in AF patients compared with the general population.2 Drug- and device-based treatments of AF may palliate but not cure this arrhythmia, and the gradual/consistent progression from paroxysmal to persistent and chronic AF has been demonstrated.3,4 Catheter ablation has increasingly been used to treat AF during this decade, although its indication should be considered carefully in each case, because it is not applicable to all AF patients. Physicians in charge and referring doctors are now required to be familiar with the selection of patients for this therapeutic modality based on knowledge of the current ablation outcome. This article summarises current ablative techniques and emphasises the appropriate application and limitations of catheter ablation for AF.
Why Is the Maintenance of Sinus Rhythm Important?
During the last several years there has been confusion about the significance of maintaining sinus rhythm in AF cases, based on a number of clinical trials. Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM),5 Rate Control versus Electrical Cardioversion for Atrial Fibrillation (RACE)6 and Strategies for Treatment of Atrial Fibrillation (STAF)7 compared the significance of rate control versus rhythm control on mortality using antiarrhythmic drugs (AAD). With an intention-to-treat analysis, no mortality differences between the two approaches were detected in these trials, leading to the conclusion that rate control is a useful treatment of rhythm control for AF. On the other hand, treatment analysis from the AFFIRM study8 showed that the presence of sinus rhythm was associated with a 47% reduction in mortality and that the use of AAD was associated with a significant increase in mortality of 49%, suggesting a potential benefit of sinus rhythm maintenance in a non-pharmacological manner.
Development of Catheter Ablation for Treatment of Atrial Fibrillation
Curative catheter ablation techniques initially attempted to mimic the lesions created by the surgical Maze procedure, resulting in limited success with a substantial complication rate. In 1998, Haissaguerre et al. first demonstrated that pulmonary veins (PVs) provided focal firings triggering the occurrence of paroxysmal AF.9 They showed that as many as 94% of such triggers originated from the PVs and that the elimination of these foci by radiofrequency (RF) energy applications in the PVs could cure the paroxysmal form of AF, which became the cornerstone of curative ablation of AF.9 However, it turned out that high recurrence rates of AF and late development of PV stenosis10 were often associated with this procedure. Subsequently, a more advanced technique attempting to isolate the PV muscle sleeves form the left atrium (LA) evolved. Among various procedures to isolate the PV muscle sleeves from the LA initially employed by several investigators, two approaches predominated: namely, segmental ostial ablation at sites where localised conductions between the PV and the LA were electrophysiologically identified,11 and anatomically guided circumferential PV ablation encircling individual PVs.12
Regardless of the different strategies, isolation of the PVs at their ostium revealed other limitations of the procedure. RF current application at the PV ostia could still cause the PV ostial stenosis,13 and the firings from the myocardium around the PV isolation area often induced the recurrence of AF.14 It was also documented that the perpetuation of AF was brought about by the re-entrant conduction between the PV and surrounding atrial tissues.15 Today, almost all centres empirically isolate all four PVs not at the ostium but outside the tubular portion of the PV to avoid the risk of venous stenosis and improve procedural efficacy. Because the PV is funnel-shaped with a large proximal end (referred to as the antrum), which blends into the posterior wall of the LA, isolation of the PV and the surrounding antral tissue has become the current goal of this procedure.
Outcome of Atrial Fibrillation Ablation in Different Strategies
Although different groups refer to the ablation procedures applied to the PV and surrounding tissue with different terminology, such as left-atrial catheter ablation,16–19 PV antrum ablation20–22 or extraostial PV isolation, the lesion sets produced by these procedures are similar (see Table 1). In spite of the different approaches, the RF energy is delivered through the tip of the small catheter (4–8mm), creating similar degrees and extent of lesions in the LA with all procedures. Therefore, most approaches are likely to yield nearly equivalent outcomes.
In the early days of AF ablation there was a wide range of success rates (from 6 to 93%),23 which caused confusion as to the interpretation and usefulness of AF ablation, especially for cardiologists, non-electrophysiological experts and general practitioners. Such large differences in efficacy in the past reports were mainly due to heterogeneous patient populations and different definitions of judgement of success depending on the operating institutions. More recent publications, in which the classification of patient population is clarified, such as paroxysmal or chronic form, and the definition of success is judged a certain time after the final procedure with AAD requirements, are clearly described. From such defined criteria, the cure rate without AAD in the paroxysmal form of AF is around 85–95% after about 1.5 times the ablation procedures.22–27 The success rate is generally lower in chronic AF than in paroxysmal AF and is around 70–85%.19,22,28,29
Electrogram-guided Ablation or Anatomical Ablation – Is Either One More Effective Than the Other?
There has been an unsettled debate concerning the requirement of electrical isolation of the PVs from the LA. The electrogram-guided ablation strategies are aimed at achieving a complete electrical disconnection of the PVs from the surrounding LA areas, with the guidance of a ring-shaped mapping catheter deployed at the ostium or antrum of the PV.11,20–22 RF energy is applied at the localised breakthrough points between the PVs and the LA. In contrast, anatomical ablation currently relies on the electro-anatomical mapping system to create a 3D image of the LA and the PVs.16–19 The position of the ablation catheter is visualised within this image, and the locations of the RF application are marked in respect of the anatomical structures. Ablative lesions are placed circumferentially around the PVs, generally encircling two ipsilateral PVs simultaneously. The end-point of the ablation procedure is to achieve a decrease in the maximum amplitude of local bipolar electrogram by ≥80% or to ≤0.1mV on the ablation line, regardless of the presence/absence of the PV disconnection.17–19 Although the proponents of both strategies have been asserting their own superiority to their opponent, they are likely to compromise their concepts. For example, the requirement of completeness in the block line around the ipsilateral PVs in the anatomical ablation has been described in order to improve the outcome30–33 and reduce the incidence of post-operative atrial tachycardia,34–38 and the circumferential RF energy applications around the PV antrum at the beginning of the procedure in the electrogram-guided approach simplify and shorten the procedure time.39 The integration of both approaches can be a step forwards for AF ablation in the near future.
Ablation Strategies Originating from Asian Experiences
In recent years experiences in AF ablation have disclosed some important and original procedures from the studies carried out in Asian countries. Iesaka et al.40 and Takahashi et al.41 proposed the method and discussed their experiences of extensive encircling pulmonary vein isolation (EEPVI), in which both ipsilateral superior and inferior PVs were isolated by an encircling continuous ablation line located at the border between the PV antrum and the LA wall at the posterior junction and on the border between the anterior PV edges and surrounding tissue, including the anterior junction. This method could be applied by monitoring the ablation site and intra-PV electrograms and evaluating the ablation catheter together with two Lasso catheters positioned in both the ipsilateral PVs. With this method both ipsilateral PVs were usually disconnected spontaneously, resulting in an 86 and 94% AF-free ratio without and with AAD, respectively. Yamane et al.22 described the efficiency of segmental PV antrum isolation with the guide of large-size Lasso catheters. They showed the feasibility and efficiency of circumferential PV antrum mapping to identify the electrical breakthrough between the LA and PVs. Segmental RF energy application, without making a linear ablation line, could electrically isolate individual PV at the antrum, resulting in an AF-free ratio of 92.7% in patients with paroxysmal AF (including 12% of cases with AAD). Kumagai et al.42 recently described the feasibility and efficiency of the box-isolation method, in which the posterior LA and all PVs were electrically isolated by a single ablation line drawn at the anterior portion of the ipsilateral PVs and the linear ablation of the LA roof, as well as the LA bottom. Complete isolation of the posterior LA was achieved in 90% of cases, resulting in an AF-free rate of 95% without AAD (all paroxysmal AF cases, after a mean of 1.1 procedures). Yao et al.43 developed a new stepwise approach, including a ‘figure of seven’ lesion line (consisting of both the roof line and the left-anterior ridge line) and additional stepwise linear lesion, depending on the response to AF termination. Among 196 AF cases (153 paroxysmal), sinus rhythm was achieved in 81.6%, with 88.3% of cases being free of AF without AADs in the subsequent observation period.
Adjunctive Ablation Strategies
In order to eliminate the substrate for maintaining AF, the efficiency of two additional strategies of PV isolation have been described. The linear lesions are commonly made at the roof between the contralateral superior PVs (roof line) and at the isthmus between the mitral valve and the left inferior PV (mitral isthmus line). This concept was based on previous reports by Hocini et al.27 and Jais et al.44 (both belong to Haissaguerre’s group), in which a combination of the roof line and the mitral isthmus line improved the AF-free ratio from 69 to 87% in paroxysmal AF cases, although epicardial RF applications were required in 60% of cases to achieve the mitral isthmus block.
Currently, the most popular method for AF substrate modification in the atrium is to apply RF energy and create lesions targeting the areas with complex fractionated atrial electrograms (CFAEs), which evolved from Nademanee et al.45 CFAEs are believed to represent slow conduction or pivot points where wavelets turn around at the end of arcs of functional blocks, and are defined as the atrial electrograms with fractionations, continuous activity or rapid firings of very short cycle length of ≤120ms averaged over a 10-second recording period. The primary end-point of ablation in their original work is either complete elimination of the area with CFAEs or conversion of AF to sinus rhythm. CFAE ablation terminated AF in 49 of 57 paroxysmal AF (86%) and 40 of 64 chronic AF (63%) patients without the use of AADs. The AF-free rate at one-year follow-up was 91% in 110 patients, including patients who underwent repeated procedures (16%). Although the concept of this method is well accepted, its role in ablation strategies has not yet been fully established. CFAE ablation targets only the substrate to perpetuate AF, and only modest efficacy of this method alone for chronic AF has been reported so far.46 More recently, CFAE ablation has been achieving a general consensus as one of the combination strategies for modifying AF substrates, as discussed below.
Sequential Multifaceted Ablation Strategy for Chronic Atrial Fibrillation
Multiple strategies of various procedures, including PV isolation, anatomy- or electrogram-guided left-atrial ablation, linear ablation and thoracic vein isolation, have been developed, as discussed above. Each strategy performed alone has been shown to yield similar rates of outcome (50–70% success), suggesting the various co-existing targets and factors as the modifiers of the AF substrates. Haïssaguerre et al.29,47,48 developed the sequential multifaceted ablation method for chronic AF, which could integrate different (electrogram- and anatomy-based) approaches. They combined the approaches of PV isolation, electrogram-based ablation targeting CFAEs, linear ablation at the LA roof and the mitral isthmus and right atrial ablation (in some cases).
Among 153 patients with chronic AF (mean duration of 22 months), termination of AF was achieved in 84% (129/153) of cases as a result of sequential ablation.48 It should be noted that regardless of the order of ablation sequences, the effect of ablation on AF termination was based on cumulative procedures. The final results after a mean of 1.6 procedures were that 95% of cases with termination of AF and 50% without AF termination during the initial ablation were in stable sinus rhythm without AAD.
Improved Safety of the Atrial Fibrillation Ablation Procedure
Complications with AF ablation include vascular complications, cardiac perforation/tamponade, valvular injury, thromboembolism, PV stenosis and injury of extracardiac tissues such as the oesophagus and nerves. According to the worldwide survey by Cappato et al.28 of 8,745 treated patients, the overall incidence of major complications amounted to 6%, including peri-procedural death (0.05%), cardiac tamponade (1.2%), stroke and thromboembolism (0.9%), PV stenosis (1.9%) and LA tachycardia (3.7%). When the reports limited to recent studies using advanced and consistent techniques are reviewed, the complication rates are lower,49 with the risk of cardiac tamponade, stroke, PV stenosis and atrioesophageal fistula at 1, 0.2, 0.2 and 0%, respectively. Advances in catheter techniques in the past decade have not only improved outcome but also reduced complication rates. For example, a highly activated clotting time level of 300–400s reduced the risk of thromboembolisms,50 RF application outside the tubular portion of the PV reduced the risk of venous stenosis, and avoidance of ablation at the atrial region closest to the oesophagus together with limiting the RF energy output can keep away from the oesophageal injury. Oesophageal injury was once focused on due to a foetal complication of AF ablation. Occurrence of the post-procedural atrial tachycardias associated with an incomplete block line can also be reduced by a complete electrical isolation of PVs at the level of the antra.34–38 Upcoming newer technologies will further improve outcome and reduce complications.
Conclusions
Rhythm control of AF in a non-pharmacological manner is of increasing importance in an ageing society. Advances in the catheter ablation technique in the last decade have provided a cure for AF patients, with almost established efficiency for paroxysmal cases. Because ablation for chronic AF cases is still challenging, early treatment for paroxysmal AF before the persistent or chronic form is mandatory. There have been a few studies so far showing the advantage of first-line RF ablation therapy in the management of AF patients.51,52 Large-scale controlled trials evaluating the effect of catheter ablation in diverse patient populations on a long-term basis are necessary for establishing the clinical guideline for its application.