Author + information
- Received February 23, 2000
- Revision received December 8, 2000
- Accepted December 28, 2000
- Published online April 1, 2001.
- Kyoko Soejima, MDa,
- William G Stevenson, MD, FACCa,* (, )
- William H Maisel, MDa,
- Etienne Delacretaz, MDa,
- Corinna B Brunckhorst, MDa,
- Kristin E Ellison, MDa and
- Peter L Friedman, MD, PhD, FACCa
- ↵*Reprint requests and correspondence: Dr. William G. Stevenson, Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115
The purpose of this study was to develop and test a new entrainment mapping measurement, the N + 1 difference.
Entrainment mapping is useful for identifying re-entry circuit sites but is often limited by difficulty in assessing: 1) changes in QRS complexes or P-waves that indicate fusion, and 2) the postpacing interval (PPI) recorded directly from the stimulation site.
In computer simulations of re-entry circuits, the interval from a stimulus that reset tachycardia to a timing reference during the second beat after the stimulus was compared with the timing of local activation at the site during tachycardia to define an interval designated the N + 1 difference. The N + 1 difference was compared with the PPI-tachycardia cycle length (TCL) difference in simulations and at 65 sites in 10 consecutive patients with ventricular tachycardia (VT) after myocardial infarction and at 45 sites in 10 consecutive patients with atrial flutter.
In simulations, the N + 1 difference was equal to the PPI-TCL difference. During mapping of VT and atrial flutter, the N + 1 difference correlated well with the PPI-TCL difference (r ≥ 0.91, p < 0.0001), identifying re-entry circuit sites with sensitivity of ≥86% and specificity of ≥90%. Accuracy was similar using either the surface electrocardiogram or an intracardiac electrogram (Eg) as the timing reference.
The N + 1 difference allows entrainment mapping to be used to identify re-entry circuit sites when it is difficult to evaluate Egs at the mapping site or fusion in the surface electrocardiogram.
Entrainment mapping is useful for guiding catheter ablation of re-entrant arrhythmias (1–4). During entrainment, pacing stimuli at a rate faster than the tachycardia continuously reset the re-entry circuit. Analysis of the surface electrocardiogram and electrograms (Egs) recorded during entrainment can be used to assess the proximity of the pacing site to the re-entrant circuit. The postpacing interval (PPI), measured from the last stimulus (S) that entrains or resets tachycardia to the next depolarization at the pacing site, represents the conduction time from the pacing site to the re-entry circuit, through the circuit, then back to the pacing site. Thus the PPI-tachycardia cycle length (TCL) difference indicates the conduction time between the pacing site and the circuit. The PPI-TCL difference is not influenced by QRS fusion during entrainment and can help identify loops in the re-entry circuit as well as isthmuses where pacing entrains tachycardia with concealed fusion (2,3). However, validity of the PPI-TCL difference is based on the assumption that the recorded Eg represents depolarization of the pacing site. Recordings from the S site are not always obtainable or interpretable due to electrical noise after the S. Alternatively, the PPI can be measured from Egs recorded by electrodes adjacent to those used for pacing, but this does introduce potential error, particularly in regions of abnormal conduction (5). The purpose of this study was to develop and test a method for determining the PPI-TCL difference that: 1) does not require simultaneous recording of the Egs at the pacing site during entrainment and 2) like the PPI is not influenced by the presence or absence of QRS or P-wave fusion (6). Specifically, we hypothesized that the PPI-TCL difference could be calculated from the conduction time between an S that entrains tachycardia and the second beat after the S (the N + 1 beat) by comparing this interval to the Eg timing at the S site in any following beat. This hypothesis was tested in computer simulations and then in patients undergoing catheter mapping of re-entrant ventricular or atrial tachycardias. Furthermore, we show that this analysis can be based either on intracardiac recordings or the surface electrocardiogram, facilitating analysis during atrial arrhythmias.
Computer simulations of figure-eight re-entry circuits were performed using a previously described model (Fig. 1)(3,7). The specified basal conduction velocities through segments in the re-entry loop (containing sites 3, 6, 24 and 27 in Fig. 1) were normal (0.6 to 0.7 m/s). In the slowest segments of the circuit (typically the common pathway from site 10 to site 1 in Fig. 1), conduction velocities ranging from 0.05 to 0.3 m/s were used. Changes from basal conduction velocities and refractory periods in response to premature stimuli are modeled as exponential functions of the diastolic interval. For re-entrant tachycardias, the effect of resetting with a single S is the same as that for a series of stimuli producing entrainment (3,7–10). Therefore, scanning single stimuli were studied for ease of analysis. Stimulation was performed from re-entry circuit sites and bystander sites. The QRS complex and Eg inscribed during or immediately after the S was defined as QRSnand Egn, respectively (Fig. 2); the following QRS and Eg were defined as QRSn+1and Egn+1, respectively. The S-QRSn+1interval and Egn+1-QRSn+2interval were determined; the difference between these two intervals was defined as the N + 1 difference.
Because the S-QRSn+1is not influenced by QRS fusion during entrainment, an endocardial Eg that is remote from the pacing site can potentially be used as the timing reference instead of the QRS onset. This hypothesis was tested by using a site in a bystander loop as the reference rather than the QRS onset.
Mapping ventricular tachycardia and atrial flutter
A retrospective analysis of entrainment data was performed from 10 consecutive patients with ventricular tachycardia (VT) due to prior myocardial infarction (10 men with a mean age of 70 ± 8 years, left ventricular ejection fraction of 35 ± 10%, tachycardia cycle length of 443 ± 80 ms during antiarrhythmic drug therapy with amiodarone in seven patients and other agents in three patients). A similar analysis was also performed using data from 10 consecutive patients with atrial flutter (eight men with a mean age of 63 ± 13 years during antiarrhythmic drug therapy with digitalis in four patients and other agents in six patients) was performed. Electrophysiologic studies and catheter ablation were performed according to protocols approved by the Brigham and Women’s Hospital Human Research Committee after informed consent was obtained. All data were digitally recorded along with a continuous 12-lead electrocardiogram (Prucka Engineering Inc., Houston, Texas). Bipolar Egs were filtered at 30 to 500 Hz. Unipolar Egs from electrodes 1 (distal) and 2 of the mapping catheter were high-pass filtered at 100 Hz. For entrainment, unipolar pacing stimuli at the distal electrode (electrode 1) was employed. Stimulus trains, starting at cycle lengths 20 to 40 ms shorter than the tachycardia cycle length and decreasing by 10 to 20 ms until capture occurred were evaluated. Sites were included for analysis if entrainment was performed at the site and either bipolar (electrodes 1–2) or filtered unipolar Egs from the distal electrode of the mapping catheter were of adequate quality to measure the PPI (5).
In 10 patients with VT, 65 sites during 18 VTs met inclusion criteria. Of 10 atrial flutter patients, six had common counterclockwise flutter, and four had other macrore-entrant atrial tachycardias; 45 sites met inclusion criteria.
Statistical analyses were performed using SAS (SAS Statistical Software Version 6.12, SAS Institute, Cary, North Carolina). Continuous data are expressed as mean ± SD. Generalized estimating equations were utilized to adjust for multiple observations in individual patients (11).
In the computer simulations, the N + 1 difference equaled the PPI-TCL difference and was 0 at re-entry circuit sites and >0 at bystander sites. To illustrate the mechanism, two examples are shown in the following text.
Re-entry circuit sites
Figure 2shows resetting by stimulation in an outer loop in the re-entry circuit (site 27). Capturing stimuli produce wavefronts that travel away from the circuit outer loop, altering the ventricular activation sequence. Hence, the morphology of QRSnis different than VT, indicating QRS fusion. The stimulated orthodromic wavefront propagates through the circuit giving rise to QRSn+1. Stimulus-QRSn+1is the time required for the stimulated wavefront to propagate from the S site orthodromically to the re-entry circuit exit (369 ms). The S-QRSn+1equals the Egn+1-QRSn+2(or the following Egn+2-QRSn+3, which indicates the conduction time over the same path). Both the PPI-TCL difference and the N + 1 difference are 0 at this re-entry circuit site. The N + 1 difference was also 0 during resetting from re-entry circuit sites in the common pathway and inner loops.
Pacing at bystander sites can entrain tachycardia with or without QRS fusion depending on the pacing site location (9). Figure 3shows resetting without fusion, by an S at a bystander attached to the common pathway (site 35). The stimulated wavefront propagates from the pacing site to the circuit, then splits into antidromic (not shown) and orthodromic wave fronts. The antidromic wave collides with a returning re-entry excitation wave and is extinguished. The stimulated orthodromic wave travels to the circuit exit producing QRSn(Fig. 3, panel A), then propagates through the circuit and back to the exit on its second revolution producing QRSn+1. QRSnand QRSn+1have the same QRS morphology as the tachycardia QRS. In the figure, x is the conduction time from the dead-end pathway to the common pathway, y is the conduction time from the junction of the dead-end pathway, through the common pathway to the exit, where the onset of the QRS occurs. Stimulus-QRSn+1is the conduction time from the site to the circuit exit plus one revolution through the circuit (x + y + TCL). In contrast, the Egn+1-QRSn+2interval is equal to the sum of the revolution time through the circuit plus (y − x). Thus, S-QRSn+1(484 ms) exceeds the Egn+1-QRSn+2(or Egn+2-QRSn+3) of 434 ms; the N + 1 difference is 50 ms. The PPI is longer than the TCL because the PPI is the conduction time from the S site to the re-entrant circuit, through the circuit and back to the pacing site. The PPI-TCL equals the N + 1 difference (50 ms). That the N + 1 difference equals the PPI-TCL difference can be shown mathematically (Appendix 1). Stimulation at bystander sites in a nondominant loop, which has a longer revolution time than the dominant loop, also produced an N + 1 difference >0 ms and equal to the PPI-TCL difference (not shown).
Furthermore, to assess the use of an intracardiac recording remote from the pacing site, rather than the QRS complex as the timing reference, activation time at a site in a bystander loop outside the re-entry circuit was analyzed. The N + 1 difference measured to activation at a site remote from the circuit was equal to the PPI-TCL difference, as illustrated in patient examples below.
Mean TCL was 443 ms. Entrainment was analyzed from 65 sites (17 with concealed fusion and 48 with manifest QRS fusion; 28 sites classified as outer loop sites) during 18 VTs. Examples of an outer loop site within the circuit and a remote bystander (9)are shown in Figure 4. In panel A, entrainment with QRS fusion is present. The PPI measured at the pacing site approximates the TCL of 355 ms, consistent with a site in the circuit. The S-QRSn+1is 370 ms, and this interval coincides with the beginning of the local Eg recorded at the pacing site (Egn+2) when the onset of QRSn+3is used as the timing reference (Egn+2-QRSn+3is 370 ms). Using the right ventricle apex as the timing reference, the S-Vn+1is 455 ms. When Vn+3is used as the reference, the point 455 ms earlier identifies the same point of the local Eg as when measured using the QRS onset as the timing reference. The PPI-TCL difference and the N + 1 difference are both zero. In panel B, pacing is performed at a bystander site. The PPI-TCL difference is 55 ms, and the N + 1 difference is 55 ms measured using either the QRS or right ventricle Eg.
There was excellent agreement between the PPI-TCL difference and the N + 1 difference measured either to the QRS (Fig. 5, panel A, r = 0.91 with p < 0.0001) or to the right ventricular apex (Fig. 5, panel A, r = 0.98 with p < 0.0001). A PPI-TCL difference ≤30 ms has previously been associated with successful catheter ablation, indicative of a re-entry circuit site (3). An N + 1 difference ≤30 ms predicted a PPI-TCL difference ≤30 ms with a sensitivity of 86% and a specificity of 90%. This agreement of the N + 1 difference with the PPI-TCL difference was similar whether pacing entrained VT with QRS fusion (48 sites, 20 bystanders, 28 outer loop sites; sensitivity 89%, specificity 90%) or without QRS fusion (17 sites, 14 in the circuit, 3 bystanders; sensitivity 82%, specificity 100%). RF current was applied at 23 sites in 12 VTs and terminated VT at seven of these sites. The N + 1 difference was not statistically different at sites with termination compared with those without termination (20 ± 28 vs. 30 ± 31 ms, p = 0.45). However, this is likely due to the inclusion of outer and inner loop sites that are in the circuit, but at broad regions where the incidence of termination is low and the relatively small number of ablation sites.
The mean flutter cycle length was 252 ms. In seven patients, the onset or peak of the P-wave was difficult to define and only the intracardiac Eg (high right atrium in three, and midcoronary sinus in four) was used as a reference. P-waves were utilized for the timing reference for 22 sites, and an atrial Eg was used for 23 sites. There was excellent agreement between the PPI-TCL difference, and the N + 1 difference measured either to the P-wave (r = 0.91, p = 0.0006) or to the atrial Eg (r = 0.94, p < 0.0001) (Fig. 5, panel B). An N + 1 difference ≤30 ms predicted a PPI-TCL difference ≤30 ms with a sensitivity of 100% and a specificity of 100%. Examples of circuit sites and a bystander site are shown in Figure 6(panels A and B, respectively).
The PPI is useful for identifying re-entry circuit sites during entrainment mapping (3). At re-entry circuit sites, the PPI approximates the tachycardia cycle length. However, analysis of the PPI is based on the assumption that the Egs indicate depolarization at the pacing site. Ideally, Egs are recorded from the mapping catheter electrodes used for stimulation, but this is sometimes difficult. Electrical noise introduced during pacing can obscure the Egs at the stimulating electrodes. Many recording systems do not allow recording from the pacing site. A previous study showed that recording from the proximal electrodes is a reasonable alternative; but error can occur, particularly if low amplitude local Egs present at the pacing site are absent at the proximal recording site (5).
Fontaine et al. (6)reported that when pacing entrained tachycardia with concealed fusion (without altering the QRS morphology as compared with the tachycardia), analysis of the S-QRS (S-QRSnin this study) could distinguish re-entry circuit sites from bystanders. This method requires that the stimulated orthodromic wavefronts exit from the circuit at the same site as the tachycardia wavefronts. Any degree of QRS fusion indicates that the stimulated wavefronts could be exiting from another route, invalidating this analysis. Ormaetrxe et al. (12)found that QRS fusion was often difficult to detect when <22% of the QRS was fused. During many atrial arrhythmias, P-wave fusion is difficult and sometimes impossible to assess. These have been the major limitations of Fontaine’s methods.
In this study, we propose a new entrainment measure, which is a modification of the S-QRS measure proposed by Fontaine et al. (6). The S-QRS is measured to the second beat, which is unquestionably due to a wavefront that has emerged from the tachycardia circuit and is not fused. Furthermore, we show that an endocardial Eg that is remote from the pacing site can be used as the reference, rather than the QRS onset. Often the endocardial recording is more precise and easily used for the fiducial point.
As with analysis of the PPI and S-QRSn, analysis of the S-QRSn+1assumes that the conduction path and time through the re-entry circuit remain the same during entrainment as during tachycardia. When conduction velocity slows during pacing, thereby prolonging the revolution time through the circuit, the PPI and S-QRSn+1lengthen, giving rise to false negative results when pacing at re-entry circuit sites. Antiarrhythmic drugs are prone to accentuate conduction slowing during entrainment. The most reliable results will likely be achieved by pacing at rates only slightly faster than the tachycardia. As with the PPI, the N + 1 analysis does not identify only narrow isthmuses in the re-entry circuit. Broad paths in the circuit, such as outer loops where entrainment occurs with QRS fusion and ablation is often difficult, are also identified. Identification of a broad path rather than a narrow isthmus is a likely explanation for the relatively low incidence of tachycardia termination during RF application, which we observed at sites predicted to be in the re-entry circuit. In the case of atrial flutter, broad paths are often reasonable targets for ablation with a series of RF lesions. In the case of re-entrant VT, identification of the outer loops in the circuit can assist in locating the region containing the circuit exit or a narrow isthmus. Successful ablation of VT by transecting a broad loop has also been reported (13,14).
The N + 1 difference allows entrainment mapping to be used even when the QRS or P-wave morphology of tachycardia is difficult to assess and when the PPI cannot be directly measured.
For dead-end pathways, the (S-QRSn+1) − (Egn+1- QRSn+2) difference equals the postpacing interval (PPI)-tachycardia cycle length (TCL) difference.
From Figure 3: × is the conduction time from pacing site to the circuit; y is the conduction time from the junction of the bystander pathway and the circuit to the circuit exit.
Therefore, the N + 1 difference = [S − QRSn+1] − [Egn− QRSn+1] = (x + y + TCL) − (y − x + TCL) = 2x
PPI = TCL + 2x
The PPI − TCL difference = PPI − TCL = 2x
Thus, N + 1 difference = PPI − TCL difference = 2x.
When the pacing site is in the re-entry circuit x = 0 and both the N + 1 difference and PPI − TCL difference = 0. Also the Egn-QRSn+1was equal to Egn+p− QRSn+p+1.
☆ Dr. Soejima was supported, in part, by a Medtronic Japan Fellowship. Dr. Delacretaz was supported by a grant from the Swiss Foundation for Grants in Medicine and Biology.
- postpacing interval
- tachycardia cycle length
- ventricular tachycardia
- Received February 23, 2000.
- Revision received December 8, 2000.
- Accepted December 28, 2000.
- American College of Cardiology
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