Hôpital Cardiologique du Haut-Lévêque, Avenue de Magellan, 33604 Bordeaux-Pessac, France and the Université Victor Segalen Bordeaux 2, Bordeaux, France
Received 23 July 2004; revised 20 October 2004; accepted 25 November 2004; online publish-ahead-of-print 6 January 2005.
* Corresponding author. Tel: +33 557 656471; fax: +33 557 656509. E-mail address: jacques.clementy{at}pu.u-bordeaux2.fr
See page 627 for the editorial comment on this article (doi:10.1093/eurheartj/ehi005)
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Abstract |
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Methods and results Twenty patients with paroxysmal AF were studied. Anatomically guided ablation was performed utilizing the CARTO system to deliver coalescent lesions circumferentially around each PV to produce a voltage reduction to <0.1 mV, with the operator blinded to recordings of circumferential PV mapping. After achieving the anatomical endpoint, the incidence of residual conduction and the amplitude and conduction delay of residual PV potentials were determined. Electrical isolation of the PV was then performed and the residual far-field potentials evaluated. Individual PV ablation was performed in all PVs. Anatomically guided PV ablation was performed for 47.3±11 min, after which 44 (55%) PVs were electrically isolated. In the remaining 45%, despite abolition of the local potential at the ablation site, PV potentials [amplitude 0.2 mV (range 0.090.75) and delay of 50.3±12.6 ms] were identified by circumferential mapping. After electrical isolation (12.2±11.7 min ablation), 55 (69%) PVs demonstrated far-field potentials; with a greater incidence (P=0.015) and amplitude (P=0.021) on the left compared with the right PVs. At 13.2±8.3 months follow-up, 13 patients (65%) remained arrhythmia-free without anti-arrhythmics. In four patients (20%), spontaneous sustained left atrial macrore-entry required re-mapping and ablation. Macrore-entry was observed to utilize regions around or bordering the previous ablation as its substrate.
Conclusion Anatomically guided circumferential PV ablation results in apparently coalescent but electrically incomplete lesions with residual conduction in 45% of PVs. Wide encircling of the PVs was associated with left atrial macrore-entry in 20% of patients.
Key Words: Atrial fibrillation Pulmonary veins Ablation Atrial flutter Electrophysiology
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Introduction |
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Electrical isolation of the PV from the atrial substance provides an electrophysiologically based endpoint that aims to prevent propagation of arrhythmogenic impulses from the PV to the atria and eliminates this region from the substrate capable of maintaining AF. Recently it has been propounded that electrical isolation of the PV may not be required and that extensive circumferential ostial ablation with a reduction in the bipolar voltage amplitude together with conduction delay across the ablation line may be adequate, resulting in an equivalent or even superior long-term suppression of arrhythmia.10 However, wider and more atrial ablation may potentially result in significantly more atrial conduction abnormalities that could support arrhythmias. In addition, incomplete lesions have been reported to be pro-arrhythmic by a number of investigators.1114 In this prospective clinical study we evaluated the acute electrophysiological consequences of anatomically guided circumferential PV ablation and subsequent clinical outcome of wide atrial ablation to isolate the PVs.
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Methods |
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Surface-electrocardiogram and bipolar endocardial electrograms were continuously monitored and stored on a computer-based digital amplifier/recorder system for off-line analysis (Bard Electrophysiology, Tewksbury, MA, USA). Intra-cardiac electrograms were filtered from 30500 Hz, and measured using on-line callipers at a sweep speed of 100 mm/s.
Radiofrequency ablation of atrial fibrillation
Prior to the ablation, all patients had effective anticoagulation for at least 1 month (INR 2 to 3) and transoesophageal echocardiography to exclude atrial thrombus.
The following catheters were introduced via the right femoral vein for electrophysiological study: (i) a steerable quadripolar catheter (Xtrem; Ela Medical, Montrouge, France) was positioned in the coronary sinus; (ii) a circumferential mapping catheter (Lasso, Biosense-Webster, Diamond Bar, CA, USA) was introduced following transeptal access and stabilized with the aid of a long sheath (Preface multipurpose, Biosense-Webster), which was continuously perfused with heparinized glucose; and (iii) a 4 -mm irrigated-tip ablation catheter (Navi Star, Biosense-Webster).
Following transeptal access, a single bolus of 50 IU/kg body weight of heparin was administered and repeated only for procedures lasting 4 h. Selective PV angiography was performed before and after ablation by hand injection of 510 mL of contrast via an NIH catheter (Cordis, Miami Lakes, FL, USA). PV diameters were calculated in the anteroposterior plane using a standard angiographic system.
Anatomical ablation of the pulmonary veins
Anatomical ablation of the PVs was performed using the technique initially proposed by Pappone et al.15 with wide encircling of the PVs without linear lesions. In brief, the procedure commenced with the creation of a baseline three-dimensional geometry of the left atrium using the electroanatomic mapping system (CARTO, Biosense-Webster). This was created using voltage/anatomical mapping during spontaneous rhythm at the start of the procedure (AF or sinus rhythm). To identify the PV, the mapping catheter was placed 2040 mm into each vein and slowly drawn back to the ostia under guidance of fluoroscopy and local electrograms. In a subset of patients the PV anatomy and ostia were verified with the use of intra-cardiac echocardiography (Acunav, Siemens Medical).
Radiofrequency (RF) energy was delivered via the distal electrode of the mapping catheter with power limited to 3040 W using irrigation rates of 520 mL/min (0.9% saline via Cool Flow; Biosense-Webster) to achieve the desired power delivery based on the reduction of the local electrogram amplitude. Temperature was limited to 50°C. Circumferential lines were created with contiguous coalescent RF lesions using a dragging technique and delivered at a distance 10 mm from the PV ostia. Circumferential ablation around the anterior aspect of the left PVs was often found to be impossible due to the narrow ridge of tissue that separates this structure from the adjacent appendage. In this case, the first part of these PVs needed to be infringed upon to achieve catheter stability, and ablation was then performed with power reduced to 2530 W. In all cases, separate ablation was performed around each vein in order to achieve coalescent applications around the PV. The endpoint of ablation was as previously described:15 (i) low peak-to-peak bipolar potentials (<0.1 mV) inside the lesion, and (ii) a delayed local activation time of >30 ms between contiguous points lying in the same axial plane across the line.
Study protocol
Prior to ablation of each PV, a circumferential mapping catheter (Lasso; Biosense-Webster) was introduced into the PV being targeted under fluoroscopic guidance. The ablation was performed with the circumferential catheter positioned within the PV but with the operator blinded to the electrograms. The operator was unblinded to the circumferential PV recordings once they had completed anatomical ablation as determined by the above endpoints. The following were determined using the circumferential mapping catheter:
If PV conduction persisted, circumferential-mapping-guided isolation of the PV (elimination or dissociation of PV potentials) was performed, targeting sites of earliest activity or polarity reversal. After completion of PV isolation, the map catheter was utilized to determine the largest amplitude of the far-field potential within the PV. Pacing techniques were utilized to distinguish local from far-field potentials, as previously described.16
Post-ablation management and follow-up
Following ablation, patients received subcutaneous heparin while oral anticoagulation was re-initiated. All patients had at least 3 days ambulatory monitoring in hospital during this time. In the absence of concurrent indications all anti-arrhythmic drugs were ceased following ablation.
Patients were hospitalized for 1 day at 1, 3, 6, and 12 months after the last procedure for assessment involving transthoracic echocardiography, ambulatory monitoring, and stress testing. At 12 months post-procedure all patients underwent CT angiography to exclude PV stenosis. After this time, in the absence of AF or symptoms, the referring physician provided follow-up data. In the event of recurrent symptomatic AF, patients were offered further ablation or trial of a previously ineffective drug therapy. In the event of a regular tachycardia, suggestive of a focal or macrore-entrant mechanism, mapping and ablation was advocated.
Statistical analysis
All variables are reported as mean±standard deviation, except variables which are not normally distributed and are described as the median and range. Comparisons were performed with either the paired or unpaired Student's t-test or the Wilcoxon signed rank or rank sum test. A KaplanMeier analysis with log-rank test was used to determine the probability of freedom from recurrent AF. Statistical significance was established at P<0.05 using a two-sided comparison.
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Results |
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Individual PV ablation was performed in all veins (separately in the single case of common left ostia) in these 20 patients, of whom 12 (60%) were in AF at the time of ablation. In this cohort, anatomical variation in the number of PVs was not observed. The total duration of RF energy, fluoroscopy, and procedural durations was 61±17 min, 49±12 min, and 187±44 min, respectively. There were no procedural complications, in particular, no patient was observed to have significant PV stenosis (defined as>50% reduction in PV diameter).
Anatomical pulmonary vein ablation (Table 2)
A total of 47.3±11 min of anatomically guided PV circumferential ablation were performed (Figure 1). At the completion of anatomically guided PV ablation, 44 (55%) PVs were electrically isolated; 11 left superior PVs (LSPVs), 11 left inferior PVs (LIPVs), 12 right superior PVs (RSPVs), and 10 right inferior PVs (RIPVs). In the remaining (n=36), despite abolition of the local potential at the ablation site, PV potentials were identified on the circumferential mapping catheter placed more distally within the PV.
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Far-field potentials
In patients with residual PV conduction, electrophysiologically guided ablation was performed for an additional 12.2±11.7 min to disconnect all PVs (Table 2). Following complete isolation of all PVs, residual far-field potentials were identified in 55 (69%) PVs with a much greater incidence (33 vs. 22 PVs, P=0.015) and amplitude [0.18 mV (range 0.051.2 mV) vs. 0.095 mV (range 0.010.65), P=0.021] in the left compared with the right PVs (Figure 3). In the RSPVs and RIPVs the mean amplitude of these far-field potentials was 0.08 mV (range 0.030.33 mV; n=13) and 0.15 mV (range 0.010.65 mV; n=9), respectively, with the far-field signal originating from either the right atrium (anterior wall of the PVs) or the posterior left atrium (posterior wall of the PVs; Figure 3A). In the LSPVs and LIPVs the mean amplitude of these far-field potentials was 0.22 mV (range 0.051.2; n=18) and 0.14 mV (range 0.050.5; n=15), respectively, with the far-field signal originating either from the left atrial appendage (anterior wall of the PVs) or the posterior left atrium (posterior wall of the PVs; Figure 3BE).
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Discussion |
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Left atrial macrore-entry after pulmonary vein ablation
While a large number of patients have now undergone PV electrical isolation for the ablation of AF, there have been few reports of the occurrence of left atrial macrore-entry. Villacastín and colleagues17 have reported two cases of left atrial macrore-entry in their 30 patients (6.6%) undergoing PV electrical isolation. In this series, recovery of conduction along the ablated PV provided the necessary substrate for macrore-entry. In their experience utilizing segmental ostial ablation to isolate the PVs, Oral et al.18 have reported a single case of left atrial macrore-entry localized to the region of the LSPV. Nakagawa et al.19 found that 9% of patients had inducible left atrial macrore-entry after PV isolation. These arrhythmias predominantly utilized isthmuses created by regions of conduction block that resulted from ablation and were successfully ablated by linear ablation to join these regions of conduction block.
In contrast, surgical compartmentalization of the atria for the cure of AF was more frequently associated with left atrial macrore-entry.13,20,21 Thomas et al.13 reported that while 91% of patients were free of AF, 96% of patients developed post-operative regular atrial arrhythmias. These authors characterized these arrhythmias in a subset of patients and found the most frequent mechanism to be one of discontinuities in the ablation line that was then capable of supporting macrore-entry. Similar evidence is also available from studies that have attempted linear atrial catheter ablation to modify the substrate for AF.11,12,14 Discontinuous or recovered conduction through these linear lesions frequently resulted in macrore-entry, which was as symptomatic as the primary arrhythmia of AF and often more sustained.
Wide atrial circumferential ablation (regardless of the presence of PV isolation) has been proposed as a method of improving the long-term success of PV ablation while reducing the potential risk of PV stenosis. The former goal was not observed in the current study, as a large proportion of patients (20%) developed spontaneous left atrial macrore-entry. Emerging evidence from other groups has also indicated that the incidence of macrore-entry with this approach is significant.22 These arrhythmias are favoured by the extensive ablation that created regions of conduction slowing and block which forms a central or lateral obstacle that is then capable of anchoring the re-entrant wavefront, forming the necessary substrate for re-entry.
Pulmonary vein electrical isolation
The anatomical approach is based on the assumption that a reduction in the voltage amplitude (to <0.1 mV) is an adequate surrogate marker of effective ablation. However, in the current study, far-field potentials were observed of greater amplitude in many cases than the criteria established for the anatomical approach. While this approach without confirmation of PV electrical isolation is reported to provide excellent results in specialized centres, it has not been reproducible by all groups.15,23 Stabile et al.24 performed the identical ablation protocol and were only able to achieve cure in 37% of patients without the use of anti-arrhythmic drugs. The associated incidence of atrial macrore-entry, particularly utilizing the mitral isthmus, is perhaps an explanation for the more recent inclusion of linear ablation at the mitral isthmus by groups advocating the anatomical approach.
There is a consensus that ablation of the PVs is better performed, where possible, from the more atrial aspect, but paradoxically some controversy has been raised about the need for PV electrical isolation. While PV isolation is a clear endpoint, incomplete isolation, defined by persisting PVLA conduction, expresses a spectrum of effects ranging from unchanged to severely damaged conduction; the end of the spectrum probably represents a satisfactory result. In the current study, anatomically guided ablation was able to eliminate the local potential but, distally within the PV, delayed potentials persisted. However, we did not evaluate the electrophysiological properties of these residual fascicles, notably in terms of their refractoriness and capability to sustain rapid repetitive activity, or the long-term clinical outcome of using the anatomical approach.
Nevertheless, all patients with recurrent AF after ablation in the current study demonstrated recovery of conduction in one or more PV, suggesting as in multiple previous studies (PV recovery 60100%),25,26 that such recovery of conduction was probably implicated in the initiation of AF in these patients. Indeed, the impact of conduction recurrence across electrically disconnected PVs using the anatomical encircling approach is not known and may play a role in the clinical outcome in these patients. The clinical need for PV isolation has been evaluated by two recent randomized studies. Oral et al.27 reported a significantly better clinical outcome with wide encircling of the PV (without an endpoint of electrical isolation) and two left atrial linear lesions than segmental isolation of the PV (using only 18 min of RF delivery for all four PVs) without linear lesions. This group has later reported a 22% incidence of left atrial flutter (Morady, Boston AF Meeting, January 2004). In contrast, Schmitt and colleagues have presented findings in 100 patients demonstrating that wide circumferential ablation was less efficient than PV isolation for the maintenance of sinus rhythm (47 vs. 71%, respectively, at 6 months, P=0.04), and indeed was associated with a 20% incidence of left atrial flutter in the former group (late breaking trials, Heart Rhythm Society Annual Scientific Sessions; San Francisco, May 2004). Recently, Pappone et al.28 observed in a prospective randomized study that the strongest predictor of recurrent arrhythmias was the presence of gaps in the PV or atrial lines.
Study limitations
While this was a prospective clinical study evaluating the prevalence of PV isolation after anatomical ablation in a small series of patients, it did not aim to determine whether PV isolation was necessary or the long-term clinical success of this strategy. Indeed, all patients who underwent anatomical ablation subsequently had ablation to achieve electrical isolation of the PV. The clinical effects of a purely anatomical PV isolation need to be evaluated in a larger series.
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Conclusion |
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Acknowledgements |
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References |
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