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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