Arrhythmia and Electrophysiology Center, Policlinico San Donato, University of Milan, Via Morandi 30, 20097 San Donato Milanese, Milan, Italy
* Tel: +39 02 5277 4337; fax: +39 02 5560 3125. E-mail address: rcappato{at}libero.it
This editorial refers to Prevalence of pulmonary vein disconnection after anatomical ablation for atrial fibrillation: consequences of wide atrial encircling of the pulmonary veins
by M. Hocini et al., on page 696
The recent discovery of a dominant role played by excitable tissues within the pulmonary veins (PVs) and at the left atriumPV junction in the initiation and possibly also the maintenance of atrial fibrillation (AF) has led investigators to develop several catheter-based strategies aimed at limiting the electrophysiological interactions between these areas and the remaining atria. Among these, two have emerged as dominant strategies in current clinical practice: one aiming at ostial segmental disconnection (OSD) of all PVs from the adjacent atrial tissue and another aiming at anatomical circumferential ablation (ACA) away from the orifice of the PVs.
OSD is best accomplished with the help of a pre-shaped circumferential multi-electrode mapping catheter advanced to the orifice of the target PV while an ablation catheter is used for radiofrequency (RF) pulse delivery at the orifice of the same PV. Using this approach, RF pulses are delivered under the guidance of the circumferential electrical activation recorded from the multi-electrode mapping catheter until no propagation of atrial impulses to the PV is observed (Figure 1A). Ablation is repeated in each remaining PV until electrical disconnection of all PVs is achieved. OSD is commonly achieved through segmental rather than circumferential ablation at the orifice of the PVs.1
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Efficacy of the two strategies
The initial results provided by pioneering centres proved that complete abolition of AF over intermediate follow-up was possible in patients with no or minimal underlying heart disease using either of the two strategies.1,2 In patients with paroxysmal AF, OSD of at least three PVs was associated with an outcome free of AF under no anti-arrhythmic drugs (AADs) in 5670% of cases following a single catheter procedure;1,3,4 the use of this strategy appeared less effective when applied to patients with persistent AF, with outcomes free of AF under no AADs as low as 22%.3 Similarly, ACA was associated with an intermediate outcome free of AF under no AADs in the range between 37 and 85% for patients with paroxysmal,2,5,6 and in the range between 28 and 65% in patients with persistent AF.6 Lower success rates than those reported by pioneering centres have recently been observed in a large series of electrophysiology laboratories replicating one or the other catheter strategies.
Regardless of the variable success rates recorded in the different laboratories, these results suggest that, despite the many factors (i.e. electrophysiological, autonomic, intra-cellular, and extra-cellular) potentially contributing to the occurrence of AF,7 complete and even incomplete electrical isolation of limited areas of excitable cardiac tissue might be sufficient to permanently abolish, at least in subsets of patients, the entire substrate responsible for this arrhythmia.
Is either of the two ablation strategies superior to the other?
To investigate the possibility that one of the two strategies may be significantly superior to the other would not only respond to a clinical necessity, but may also help to shed further light on our understanding of the mechanisms that underlie human AF. Indeed, the two proposed strategies are based on a different rationale, require different methods, and aim for different endpoints. Aiming for OSD implies that most, if not all of the arrhythmogenic activity responsible for AF is confined within the PVs; the methods to achieve this endpoint are easily reproducible, the success of the investigator's effort can easily be assessed in the context of the procedure and about 100% of targeted PVs can be isolated.1,3,4
Conversely, aiming for ACA is based on the assumption that the atrial tissue adjacent to the orifice of the PVs is also involved in the mechanisms responsible for AF. As a consequence, ablation around segments of peri-venous atrial tissue becomes a relevant part of the strategy up to the point that electrical isolation of areas surrounded by the ablation line is not mandatory as long as significant abatement of local potential and/or consistent local conduction delay are achieved. Although this ablation design reflects the investigators' belief that electrical isolation is not required for a favourable outcome in patients receiving ACA, it should be recognized that the endpoints identified to achieve the final design nicely match with the objective difficulty to obtain transmural contiguous lesions away from the PV orifice.
Despite the value of the innovative concept proposed by the investigators introducing ACA, the challenge of surrounding a variable amount of potentially arrhythmogenic atrial tissue (together with PV excitable tissue) within an ablation line appears to be hampered by a number of factors. These include the arbitrary location of the boundaries of the ablation line, the large amount of ablated substrate (increasing as the radius of the intended circumferential ablation line is increased!) and the fragility of the endpoints. It is not surprising, therefore, that different catheters (4 mm tip, 8 mm tip, irrigation, or cooled-tip) are used with different ablation designs and power-sets in different centres using the same strategy.2,5,6 As a consequence, it is reasonable to assume that the long-term outcome in patients receiving ACA is more operator dependent than in patients receiving OSD.
How to compare the two ablation strategies
A most appropriate method to investigate reliably whether one of the two ablation strategies is superior would be to compare the outcome of patients with similar entry criteria undergoing prospective random assignment to OSD or ACA. Using this method in patients with paroxysmal AF presenting with a left atrial diameter of 55 mm and a left ventricular ejection fraction of
0.35, Oral et al.8 recently showed that, during the 6 months following a single catheter procedure, ACA was associated with a significantly better outcome (35 of 42 patients free of AF under no AADs) than OSD (27 of 40 patients free of AF under no AADs) with no differences between the two ablation strategies in the complication rates. Although the unique value of such a study should be recognized, the single-centre nature of the study, the absence of a pre-defined working hypothesis, the relatively short follow-up, and the low number of patients included should encourage caution before we can extrapolate these results to a more general population of similar patients.
Based on the observations mentioned above, it is not surprising that in another prospective randomized study comparing the two strategies, Schmitt et al.9 reported opposite results to those of Oral et al.8 At 6-month follow-up, these authors showed that maintenance of stable sinus rhythm was significantly more frequent in patients (33 of 50) receiving OSD than in patients (21 of 50) receiving ACA. These results await peer review confirmation. Not unexpectedly, the opposite results in the two studies were obtained because of the large variability in the success rate observed in patients undergoing ACA (88 vs. 47%) while the success rates in patients undergoing OSD remained unchanged (67 vs. 71%).
Is complete electrical isolation within areas surrounded by ablation lines required for a better outcome?
Despite the considerable volume of data collected in patients undergoing catheter ablation of AF during recent years, we must recognize that the question addressed in the title of this paragraph remains unanswered.
In patients receiving OSD, there is evidence that short-term efficacy can occasionally be observed in the presence of conduction recurrence across all previously disconnected PVs;10 in such cases, it is possible that the extent of conduction delay developed in response to the changes induced by chronic lesions prevents, at least for some time during follow-up, the occurrence of arrhythmia relapses. Conversely, patients with recurrence of AF invariably show conduction recurrence across one or more previously disconnected PVs.1,3,4 This observation raises the question of whether systematic re-disconnection alone would be sufficient or whether an enlarged design inclusive of additional ablation lines11 should be considered in order to cure these patients. Of note, there is no evidence to date of post-ablation AF recurrence in the presence of documented persistent isolation of all previously disconnected PVs.
In patients receiving ACA, the data available are even less clear. On the one hand, the use of an empirical approach to the technique of RF pulse deployment in the left atrium offers an attractive method to ease the applicability of this strategy over large numbers of centres. On the other hand, there are no systematic studies that may help us to interpret the possible causes of arrhythmia recurrence or occurrence of new arrhythmias,2,5,6,8 and to apply corrective techniques.
A first attempt to a more systematic interpretation of the changes produced by ACA is provided by Hocini et al.12 In their study, coalescent RF lesions were delivered through the tip of an irrigated catheter around the PVs of 20 patients with paroxysmal AF to produce, at each site, a voltage reduction to <0.1 mV and/or a local activation time of >30 ms between contiguous points along the ablation line.2 Using these criteria, the authors proved that only 44 out of 80 (55%) PVs became electrically disconnected and that the ability to achieve voltage reduction to <0.1 mV of the potential recorded at the tip of the ablation catheter was usually prevented by the influence of the far-field signal. Isolation of the remaining 36 PVs was performed by means of ostial electrical disconnection. During 13.3±8.3 months follow-up, four out of seven (20%) patients with arrhythmia recurrence developed left atrial flutter.
Thanks to the study by Hocini et al.12 we now know that, using the ACA strategy according to the classical recommendations, electrical disconnection of the segment surrounded by the ablation lines can be expected in about half of the target areas, although we still do not know in how many patients this result is to be expected for all four target areas (a situation which would most closely resemble the one observed in patients receiving OSD!). We also now know that abatement of local potentials to <0.1 mV may not be possible in some areas; in these cases, investigators should not persist with aggressive ablation protocols at the expense of an increased risk of complications.13 Unfortunately, the study design prevents the possibility of investigating whether the presence and the number of isolated segments in the single patient can be predictive of clinical outcome. Another relevant question which remains unanswered after this study relates to the rate of conduction recurrence across electrically disconnected segments late after ablation and its influence on clinical outcome. Previous studies in patients receiving OSD have shown that conduction recurrence may occur in up to 80% of the PVs 45 months after ablation;10 the width and the thickness of the target substrate in patients undergoing ACA may well represent a condition in which conduction recurrence across one or more conduction gaps is to be expected not infrequently. Finally, the study confirms that left atrial flutter is a rather common adverse event occurring late after ablation, providing a contributing role among the causes leading to failure of ACA.
In a recent study, Ouyang et al.14 showed that complete disconnection of all PVs can be achieved in the majority of patients 12 cm away from the orifice using a catheter technique which combines the characteristics of OSD and ACA. The technique consists in the advancement of two pre-shaped circumferential multi-electrode mapping catheters, each located at the orifice of the two ipsilateral PVs. After left atrial electro-anatomical reconstruction using the same strategy as with ACA, coalescent subsequent circumferential RF pulses are delivered around the two PVs several millimetres away from their orifices by means of the same mapping catheter using an irrigated ablation mode. RF pulses are delivered until electrical disconnection of both ipsilateral PVs is achieved. ACA is then repeated using the same method around the two remaining ipsilateral PVs.
Using this technique, Ouyang et al.14 could successfully disconnect all PVs in 41 patients with paroxysmal or persistent AF during 178±30 days; recurrence of atrial arrhythmias was observed in 10 patients. After a second procedure in 25% of the patients, the authors report an outcome free of AF under no AADs in 39 out of 41 patients. The data of this study suggest that electrical isolation of critical segments within the left atrium may be very effective, possibly more effective than ACA, in the curative treatment of AF. Although this study does not help to clarify whether electrical disconnection is more effective when achieved at the orifice (OSD) of the PVs or several millimetres away (ACA), it nevertheless provides a valuable model for future investigations in this direction.
OSD and ACA continue to represent reasonable alternative strategies for the curative treatment of selected categories of patients with AF. To date, there is no conclusive evidence that one strategy should be preferred to the other; also, we still do not know whether complete isolation is superior to incomplete isolation, and where isolation should best be accomplished to optimize the clinical results. This is mainly related to limits of the two strategies and to the lack of solid comparative data. The late occurrence of left atrial flutter may considerably impair the efficacy of ACA, and systematic strategies for limitation and cure of this adverse event are under investigation. Recent developments promise to disclose more effective tools which may help investigators to provide conclusive answers to the many questions still open in this field.
Footnotes
References
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