DISCUSSION.
In several recent studies, LA bipolar endocardial voltage maps constructed by acquiring thousands of voltage points by means of 3d-S (19 ) have emerged as a tool for defining AF substrates during RF ablation procedures (20 ). Indeed, LV has been considered a surrogate marker of the presence of atrial fibrosis, and may play a role in giving rise to the mechanisms underlying AF, especially in the case of PsAF (21,22 ). In these studies, however, mapping strategies and definitions of LV areas were heterogeneous. The electrical signals recorded by catheters are converted by 3d-S into color-coded voltage maps. These maps, however, may vary according to the catheters and 3d systems used. The problem is that several non-substrate factors can theoretically influence electrogram voltage (23,24 ).Activation direction, electrode spacing, electrode size, filter settings, point density and tissue contact are all factors that potentially influence HD maps; the technical challenges raised by these factors were discussed in a very interesting paper by Sim et al. (25 ). In particular, the relationship between the orientation of the recording bipole and the wave-front bipole may influence the arrival time of the activating wave-front at each electrode. A solution to this problem may be provided by a new mapping technique, known as omnipolar mapping; this is based on the use of a 3d mapping system and a multi-electrode catheter that allows simultaneous recordings of unipolar electrograms, and which spans 2d and 3d space to derive conduction velocity and wave-front direction (26 ). Omnipolar mapping therefore enables detailed characterization of myocardial activation in a way that is insensitive to catheter orientation; thus, the use of OC and -Ensite-Precision may be able to improve the detection of abnormal atrial substrate by using electrogram amplitude characteristics. Identifying LV areas also depends on the recording window specified for analysis and on the related voltage thresholds chosen for the definition of LV, since these factors can cause HD maps to vary markedly. Data on the relationships between pre-ablation atrial fibrosis and atrial voltage thresholds are not currently available, and no true voltage threshold for atrial anomalies has been established. However, most studies have used a voltage amplitude <0.05 mV to identify scar areas and a value of >0.5 mV to identify normal tissues, while the range between 0.05 and 0.5mV is commonly used to define the LV that identifies the presence of underlying anomalies in the atrial structure. In our study, we chose the 0.05-0.5 mV range adopted in several studies that have used CARTO and Ensite-Precision, in order to construct HD maps through the recording of electrical signals acquired from the CMC LassoNav, CMC AFocus or MC. For HD maps acquired by means of Ensite-Precision and OC, we identified a range of LV that was more suited to representing atrial fibrosis. This was because Ensite-Precision and OC differ from CARTO and MC in terms of their ability to select the bipolar electrograms. Indeed, by comparing different orientations of bipolar electrograms from the OC electrode, omnipolar electrograms acquired by means the same catheter match those of the largest bipolar electrogram, thereby eliminating the influence of reduced amplitude due to activation direction (11,13 ). This relative increase in electrogram amplitude has been shown to change the voltage threshold by which tissue can be histologically defined as scar. This concept was demonstrated by a recent study on ventricular myocardial voltage, which reported that, when performing omnipolar mapping, adopting a scar threshold of 1.5 mV (a value far higher than the standard 0.5 mV for conventional bipolar mapping) corresponded better to electrophysiologist-determined scar than the area determined from bipolar signals (27 ). Additionally, Takigawa et al. explored the optimal threshold in 2 configurations of OC in 6 infarcted sheep, and compared the impact of electrode spacing and bipolar direction on the scar threshold (28 ). They found that, although scar areas were well distinguished from areas of healthy tissues in any bipolar configurations with OC, bipolar spacing of 1 mm showed relatively lower accuracy, and bipolar voltages generally increased as the inter-electrode spacing increased in both healthy and scar areas. It has also been shown that LV areas documented by OC and HD-wave configuration during VT ablation procedures are smaller than the same areas identified by means of the “along” and “across” bipolar configuration (29 ). Substrates in the LA of patients with AF are probably similar to, but not the same as, scar tissue due to infarction of the ventricular myocardium. It has been suggested that re-entry mechanisms do not occur in densely fibrotic areas or scar tissue because there are not enough cardiomyocytes to allow impulse propagation (30 ), nor does it occur in mostly normal tissue, because any re-entry circuits that are established are unstable and self-terminate promptly. We identified anatomical areas characterized by a set of different colors (green/red/yellow/blue/gray/purple). To do so, we used the best duplicate algorithm of Ensite-Precision, after setting an optimal voltage range, and the OC of 16 electrodes with 3 mm inter-electrode spacing, which is the optimal spacing according to the results of the study by Takigawa. In our view, this approach offers a simple method of searching for potential and selective electro-anatomical substrates underling AF, and probably constitutes the basis of truly tailored ablation. Indeed, our approach, which was both qualitative and quantitative, helped us to identify potential patchy fibrosis; thus, it was probably able to define a substrate that could represent local non-PV conductive alterations that influence anisotropy. This substrate probably plays a critical role in giving rise to AF mechanisms, as described by some authors (31,32 ). We used the OC to search for the range that could best identify this substrate. This revealed that increasing the range from 0.05–0.5 mV to 0.5–1 mV increased the possibility of observing electrical alterations compatible with patchy fibrosis. By contrast, if bipolar signals are used, this capacity is lost, as scar tissue is more evident, and this probably does not express true electrical alterations. The optimal range of 0.3-0.6 mV that we identified characterized the non-PV substrate more selectively than the range reported in the literature. Finally, the results from our quantitative analysis of the substrate identified by means of OC and the optimal range were similar to those reported by Masuda et al. (33 ). These authors compared “along” and “across” CMC bipolar HD maps with OC omnipolar HD maps, and found a significantly lower percentage of LV areas in the majority of LA anatomical areas studied by means of OC than in those evaluated by means of bipolar HD maps. In our experience, the total number of voltage points acquired was significantly higher with OC than with MC, thus allowing us to construct maps with higher density. These findings are also in line with those of Masuda. Moreover, the procedural time needed for the acquisition of voltage points was similar among the different catheters used; this was probably due to the fact that more complex mapping is required in patients with PsAF, in whom OC were preferentially used, while CMC mapping yielded fewer voltage point.
Limitations. This study has some limitations. Firstly, it was single-center and retrospective; future studies should be prospective and multi-center and include direct comparison of diagnostic catheter technologies in a randomized setting. Moreover, only a small number of patients were included, while larger series are needed in order to fully assess the efficacy of 0.3 mV as the lower and 0.6 mV as the upper cut-off limits when OC are used to identify substrates that may play a role in maintaining AF. In addition, our search for LV was arbitrarily performed only during sinus rhythm and no comparison was made during AF; the superiority of the sinus rhythm approach therefore remains to be validated. Finally, we did not evaluate the impact,in terms of outcome, of tailored RF ablation of the substrates identified by means of OC in comparison with a matched control group of patients in whom the substrates were identified by means of MC.
CONCLUSION.
According to our experience, the combined use of OC and Ensite-Precision selectively identifies substrates that are potentially responsible for the mechanisms of AF by detecting LV that are not affected by the orientation of the catheter with respect to the activating wave-front. This approach therefore overcomes one of the limitations of using HD maps derived from bipolar catheters. In our study, the 0.3-0.6 mV range associated with a qualitative analysis identified potential fibrotic substrates that could play a role in the mechanism of sustained AF better than the standard range of 0.05 - 0.5 mV. However, further studies are needed in order to determine whether 0.3- 0.6 mV is the optimal range within which to identify LV areas by means of OC and Ensite-Precision.
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