Author + information
- Received October 30, 2017
- Revision received January 16, 2018
- Accepted January 31, 2018
- Published online July 16, 2018.
- Hiroyuki Ito, MDa,∗ (, )
- Nitish Badhwar, MDb,
- Akash R. Patel, MDc,
- Kurt S. Hoffmayer, MD, PharmDd,
- Joshua D. Moss, MDb,
- Cara N. Pellegrini, MDb,e,
- Vasanth Vedantham, MD, PhDb,
- Zian H. Tseng, MDb,
- Ronn E. Tanel, MDc,
- Henry H. Hsia, MDb,e,
- Randall J. Lee, MD, PhDb,
- Gregory M. Marcus, MD, MASb,
- Edward P. Gerstenfeld, MDb and
- Melvin M. Scheinman, MDb
- aDivision of Cardiology, Department of Medicine, Showa University, Tokyo, Japan
- bSection of Cardiac Electrophysiology, Division of Cardiology, University of California, San Francisco, San Francisco, California
- cDivision of Pediatric Cardiology, Department of Pediatrics, University of California, San Francisco, San Francisco, California
- dSection of Electrophysiology, Division of Cardiology, University of California, San Diego, San Diego, California
- eSan Francisco VA Medical Center, San Francisco, California
- ↵∗Address for correspondence:
Dr. Hiroyuki Ito, Division of Cardiology, Department of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan.
Objectives This study hypothesized that early coupled ventricular extrastimuli (V2) stimulation might yield a more robust differentiation between atrioventricular nodal re-entrant tachycardia (AVNRT) and atrioventricular re-entrant tachycardia (AVRT).
Background Programmed V2 during supraventricular tachycardia are useful to differentiate AVNRT from AVRT by subtracting the ventriculoatrial (VA) interval from the stimulus to atrial depolarization (stimulus atrial [SA]) interval, but all such maneuvers have limitations.
Methods Patients with either AVNRT or AVRT were investigated. The entire tachycardia cycle length (TCL) was scanned with V2 delivered from the right ventricular apex. The SA−VA difference was calculated with V2 clearly resetting the tachycardia. The prematurity of V2 was calculated by dividing the coupling interval (CI) by the TCL.
Results A total of 210 patients (102 with AVNRT) were included. The SA−VA difference was >70 ms in all AVNRT patients and was <70 ms in all AVRT patients with right and septal accessory pathways (APs), except for those with decremental APs, in whom there was an overlap between AVNRT and AVRT with left APs. However, a SA−VA difference >110 ms with a CI/TCL of <65% distinguished AVNRT from AVRT using the left AP, with sensitivity and specificity of 87% and 100%, respectively. Ventricular overdrive pacing resulted in tachycardia termination or AV dissociation in 28% of patients compared with 15% of patients using the V2 technique (p = 0.008).
Conclusions A SA−VA of >70 ms using the V2 technique differentiated AVNRT from AVRT using septal and right APs. Use of the V2 technique with a short CI differentiated AVNRT from AVRT using left APs. The V2 technique less frequently resulted in tachycardia termination compared with ventricular entrainment.
- coupling interval
- premature ventricular extrastimulus
- supraventricular tachycardia
- ventricular entrainment
- ventriculoatrial interval
Various maneuvers have been reported to differentiate the mechanism of supraventricular tachycardias. Ventricular entrainment is one of the most useful maneuvers to identify atrial tachycardia by confirming the atrial-atrial-ventricular response (1) and to distinguish atrioventricular nodal re-entrant tachycardia (AVNRT) from atrioventricular re-entrant tachycardia (AVRT) by using the difference between the stimulus atrial (SA) interval after ventricular entrainment and the ventriculoatrial (VA) interval during tachycardia or using the difference between the post-pacing interval (PPI) and tachycardia cycle length (TCL) (2–4). However, this maneuver often results in termination of the tachycardia or in AV dissociation, which has been found to occur in 5% to 65% of patients (5–9). By contrast, it has been reported that determination of SA−VA after resetting with ventricular extrastimuli (V2) is also useful in differentiating AVNRT from AVRT, but there is still overlap in this parameter between AVNRT and AVRT using a free wall accessory pathway (AP) (10). Although many maneuvers have been described to differentiate AVNRT from AVRT, all of them have limitations.
The purpose of this study was to test these hypotheses: 1) whether programmed right ventricular (RV) V2 that reset the tachycardia would be equivalent to or superior to ventricular entrainment to distinguish AVNRT from AVRT; and 2) whether the use of early coupling intervals (CIs) might enhance differentiation of AVNRT from AVRT.
Consecutive patients with AVNRT or AVRT who underwent electrophysiological studies in participating centers between January 2012 and August 2016 were investigated (prospectively after April 2015). Patients were excluded if there were ≥2 tachycardia mechanisms, tachycardia was not sustained, or TCL varied >30 ms. Patients with antidromic AVRT were also excluded. We evaluated clinical characteristics, including age, sex, body mass index, ejection fraction, and presence of cardiac disease.
Electrophysiological studies were performed using standard techniques after obtaining written informed consent. All antiarrhythmic drug therapies were discontinued at least 5 half-lives before the procedure. Quadripolar electrode catheters were inserted into the femoral vein and positioned in the high right atrium, anteroseptal tricuspid valve (His bundle recording), and RV apex. A decapolar electrode catheter was also inserted into either the femoral vein or the internal jugular vein and positioned in the coronary sinus (CS). Twelve-lead surface electrocardiograms and intracardiac electrograms were recorded and stored on the Prucka CardioLab (GE Healthcare, Little Chalfont, United Kingdom) recording system. Bipolar intracardiac electrograms were filtered between 30 and 500 Hz and recorded at a speed of 100 mm/s. Bipolar pacing was performed at twice the diastolic threshold from the distal electrode pair.
Tachycardia was induced by programmed stimulation from the RV apex and the high right atrium. If the tachycardia was not inducible or not sustained at baseline, isoproterenol was infused continuously to accelerate the sinus rate by >20% or to a sinus rate >100/min, and programmed stimulation was repeated. Atrial tachycardia was excluded by the presence of a ventricular-atrial-ventricular response after RV entrainment of the tachycardia. The diagnoses of AVNRT or AVRT were made according to conventional electrophysiological criteria (4,6), and the results of a successful ablation site. Patients were defined as having a slowly conducting AP if the VA/TCL was ≥40%; they were also defined as having a nondecremental AP if the VA/TCL was <40% (11). AP sites were divided into right-sided, septal, and left free wall pathways.
Entrainment of the tachycardia was attempted with RV apical pacing at a cycle length of 10 to 30 ms shorter than the TCL. Entrainment was confirmed when the atrial cycle length was accelerated to the pacing cycle length with the same atrial activation sequence, and the tachycardia resumed after stopping the pacing train. The V2 technique was performed by delivering a single RV extrastimulus starting from a CI 10 ms shorter than the TCL. The CI was decreased in 10-ms steps until resetting occurred or the ventricular effective refractory period was reached. Resetting was confirmed when the atrial depolarization following V2 was advanced or delayed by at least 10 ms without termination of the tachycardia. V2 with the shortest CI was used as the primary value for measurement.
Measurements and definitions
The SA interval was measured from the RV stimulus to the rapid deflection of the earliest reset atrial electrogram on the high right atrium or CS recording, whichever was more clearly seen during the tachycardia (Figures 1A and 1B). The VA interval was measured from the onset of the surface QRS complex to the rapid deflection of the atrial electrogram during tachycardia on the same electrode that was used for measurement of the SA interval. The SA−VA difference (SA−VA [V2]) was calculated by subtracting the VA interval during supraventricular tachycardia from the SA interval obtained by using V2 technique. The PPI was defined as the interval from the stimulation spike on the RV electrode to the rapid deflection of the next sensed ventricular electrogram on the same electrode.
For statistical analysis, all analyses were performed using JMP pro 11 for Windows (SAS Institute Inc., Cary, North Carolina). Continuous variables were expressed as the mean ± SD, and compared using the Student t test or Mann-Whitney test as appropriate. Nominal variables were compared by Pearson chi-square analysis. Optimal cutoff values of selected continuous variables to diagnose the tachycardia were determined by receiver-operating characteristic curve analysis. Sensitivity, specificity, and positive and negative predictive values and their corresponding 95% confidence intervals were calculated. A p value of <0.05 was considered statistically significant.
The V2 technique was successfully performed in 210 patients with AVNRT or AVRT (prospectively in 91 patients and retrospectively in 119 patients). Of these, there were 113 (53%) men and 99 women, and their mean age was 36.5 ± 22.0 years. There were 5 (2%) patients with coronary artery disease and 28 (13%) patients with hypertension.
AVNRT was diagnosed in 102 patients, whereas AVRT was diagnosed in 108 patients. Clinical characteristics of each group are shown in Table 1. The patients with AVNRT were significantly older and had a higher body mass index than those with AVRT. The percentages of hypertension and hyperlipidemia were significantly greater in patients with AVNRT.
Electrophysiological diagnosis and values in the study group
Electrophysiological study revealed typical (slow-fast) AVNRT in 97 patients, atypical (fast-slow) AVNRT in 5 patients, and AVRT with a slowly conducting AP in 8 patients (3 left, 4 septal, and 1 right APs). The other 100 patients with AVRT showed nondecremental VA conduction (46 left, 36 septal, and 18 right APs).
Electrophysiological data are shown in Table 2. During tachycardia, TCL was significantly longer and the VA interval was significantly shorter in those with AVNRT than in those with AVRT (388 ± 65 ms vs. 332 ± 59 ms and 68 ± 66 ms vs. 157 ± 53 ms, respectively; p < 0.001).
SA−VA difference and the PPI−TCL using the V2 technique
The results of V2 technique are also shown in Table 2. The SA−VA (V2) was significantly longer in those with AVNRT than in patients with AVRT (125 ± 24 ms vs. 58 ± 35 ms; p < 0.001). PPI–TCL (V2) was significantly longer in patients with AVNRT than in those with AVRT (142 ± 34 ms vs. 95 ± 41 ms; p < 0.001).
In all patients with AVNRT, including those with atypical forms, SA−VA (V2) was >70 ms, whereas it was <70 ms in all patients with AVRT using right APs and septal APs (Figure 2A). Furthermore, SA−VA (V2) <45 ms was not seen in patients with AVNRT, in patients with AVRT using left APs, and in patients with AVRT that used the slowly conducting AP, which narrowed the diagnosis to AVRT using a right or septal nondecremental pathway. By contrast, there was wide overlap in PPI−TCL (V2) between the tachycardia mechanisms (Figure 2B).
Relationship between the SA−VA difference and the CI/TCL ratio
The relationship between the SA−VA and CI/TCL ratio using the V2 technique is shown in Figures 3A and 3B. Eight patients with AVRT that used the slowly conducting AP were excluded due to marked irregularity in their SA−VA differences (127 ± 57 ms). There was a significant negative correlation between SA−VA and the CI/TCL ratio for both AVNRT and AVRT regardless of the AP location. SA−VA with a cutoff of 70 ms differentiated AVNRT from AVRT using right and septal APs, regardless of the CI. There was overlap between AVNRT and AVRT using the left APs, but the increase in the SA−VA (V2) was steeper for those with AVNRT. The receiver-operating characteristic curve analysis revealed an optimal SA−VA (V2), with a cutoff of >110 ms with a CI/TCL ratio of <65% that served to best differentiate AVNRT from AVRT using a left AP with sensitivity, specificity, and positive and negative predictive values of 87%, 100%, 100%, and 66%, respectively (Table 3).
Results of ventricular entrainment
There were 145 patients who underwent successful ventricular entrainment, and ventricular-atrial-ventricular response was observed in all these patients. The SA−VA difference after ventricular entrainment was >85 ms in all AVNRT cases, and <85 ms in all AVRT cases with right and septal APs (Figure 4A). PPI−TCL was >115 ms in 75 of 80 patients with AVNRT and <115 ms in all patients with right or septal APs (Figure 4B). However, there was overlap between the AVNRT and AVRT that used left APs and between AVNRT and AVRT that used slowly conducting APs. Ventricular overdrive pacing resulted in termination or AV dissociation in 5 of 8 patients with AVRT that used slowly conducting APs.
Ventricular overdrive pacing resulted in tachycardia termination or AV dissociation in 28.9% of patients, compared with the V2 technique in 15.6% of patients (p = 0.005).
We tested a novel maneuver using programmed V2 during supraventricular tachycardia to distinguish AVNRT from AVRT. As a result, we found that an optimal SA−VA (V2) cutoff was >70 ms to distinguish AVNRT from AVRT using right and septal APs, and that SA−VA (V2) <45 ms was a good cutoff to exclude AVNRT and AVRT using left APs and slowly conducting APs. In addition, there was statistically significant negative correlation between SA−VA and the CI/TCL ratio in both AVNRT and AVRT, and SA−VA (V2) >110 ms with a CI/TCL ratio <65% was useful to differentiate AVNRT from AVRT using left APs, with sensitivity and specificity of 87% and 100%, respectively. In addition, V2 was less likely to cause termination of tachycardia or AV dissociation compared with ventricular entrainment.
Several reports described the diagnostic value of RV extrastimuli during supraventricular tachycardia. Zipes et al. (12) found that a RV extrastimulus during the His refractory period reset supraventricular tachycardia if an AP was present. Miles et al. (13) reported the importance of the pre-excitation index in response to a RV extrastimulus to identify the presence of a left free wall AP. Packer et al. (14) reported the ability and number of RV extrastimuli to reset supraventricular tachycardia to identify the location of the AP using the pre-excitation index. This index was also helpful for differentiation of AVNRT from AVRT.
The SA interval is the time period for conduction from the stimulation site to the atrium via retrograde AV node conduction in AVNRT and reflects the conduction time from the site of ventricular stimulation to the atrium via retrograde AP conduction in orthodromic AVRT. Therefore, the results of the SA−VA difference using the V2 technique should be as useful as those using ventricular entrainment. Weiss et al. (15) reported that the SA−VA difference after reset with a RV extrastimulus was longer in those with left free wall APs than in those with septal APs, but they did not show a clear cutoff value and did not distinguish right free wall APs from AVNRT. García-Fernández et al. (10) found that the SA−VA difference after reset with single or double RV apex extrastimuli was useful to differentiate AVNRT from AVRT. However, they combined left and right free wall AP results, and there was overlap between free wall APs and septal APs versus AVNRT. There was also overlap between AVNRT and AVRT using left APs in the present study. It was reasonable that both the SA interval and the SA−VA difference in AVRT using a left AP would be longer, because the left AP is farther from the stimulation site than right or septal APs if the stimulation is delivered from the RV apex.
Generally, it is more challenging to distinguish AVNRT from AVRT using septal or right APs than from AVRT using left APs, because the latter can be identified by the activation sequence of CS electrodes. The simple criterion of the SA−VA difference with a cutoff of <70 ms is reliable in distinguishing AVRT, using septal and right APs, from AVNRT. Furthermore, the SA−VA <45 ms makes this diagnosis more robust compared with AVRT using a left AP and a slowly conducting AP.
We did not find a clear cutoff of PPI−TCL (V2) for distinguishing AVNRT from AVRT, regardless of the AP location. A previous report showed that there was a significant overlap of PPI−TCL among AVNRT, free wall AVRT, and septal AVRT (7). They suggested the importance of correcting PPI−TCL by subtracting AV nodal conduction time from the PPI−TCL difference. The results of the present study showed that resetting the tachycardia with V2 was preferable to using the PPI−TCL to separate AVNRT from AVRT.
Coupling interval and the SA−VA difference
There are no previous reports that describe the relationship between the CI of the extrastimulus and the SA−VA difference. We found that there was a negative correlation between SA−VA and the CI/TCL ratio for AVNRT and AVRT. For those with AVRT using septal and right APs, SA−VA (V2) was always <70 ms, regardless of CI. In the same way, SA−VA (V2) was always >70 ms, regardless of CI in AVNRT. Although there was overlap between AVNRT and AVRT using left APs, SA−VA (V2) with a short CI was able to better differentiate between mechanisms by using the magnitude of change in differences at a shorter CI. We postulated that this difference was explained by the decremental nodal conduction in AVNRT compared with that of AP-mediated tachycardia. In general, the diagnosis of AVRT with a left AP was easier than that of septal or right APs by considering the atrial activation sequence on the CS catheter, but this simple maneuver could be achieved even without use of a CS catheter. It is noteworthy that some laboratories do not use the CS catheter at the start of the procedure, and in some countries, cost becomes an important factor in the number of catheters that are used.
Programmed stimulation versus ventricular entrainment
Michaud et al. (4) reported that the SA−VA difference and PPI−TCL after ventricular entrainment were useful in differentiating atypical AVNRT from AVRT using a septal AP. González-Torrecilla et al. (2) found that the SA−VA after ventricular entrainment was useful in differentiating atypical AVNRT from AVRT, regardless of the AP location. Akerström et al. (3) reported that the maneuver was useful in all patients with supraventricular tachycardia. There is no doubt that ventricular entrainment is useful to diagnose supraventricular tachycardia if it is successfully performed without tachycardia termination or AV dissociation. A previous report found that entrainment could not be achieved in 15.2% of tachycardias because of tachycardia interruption, whereas extrastimuli from the RV could be achieved in 99.5% (10). In the present study, the percentage of the cases with evaluable data was significantly greater with V2 compared with ventricular entrainment. Ventricular overdrive pacing may cause termination of the tachycardia if an impulse blocks in the orthodromic direction and collides with the antidromic direction with the previous beat.
There were similar overlaps between AVNRT and AVRT with a left AP in both techniques. It was reasonable that the SA interval, SA−VA difference, PPI, and PPI−TCL were greater in patients with left APs than in those with right or septal APs because the distance and conduction time from the stimulation site in the RV to the atrium are greater in those with left APs compared with other sites. Therefore, the SA−VA in AVRT with the left AP was more likely to overlap with that in AVNRT compared with AVRT with right or septal APs. However, use of the V2 technique with the earliest CI effectively separated left-sided AP from AVNRT.
AVRT using slowly conducting AP
In the study by Michaud et al. (4), 29 of 44 patients with AVRT using a septal AP had a long RP (R wave to P wave) interval tachycardia, and all of them had both the SA−VA difference of <85 ms and the PPI−TCL of <115 ms. However, Bennett et al. (11) found that the ventricular entrainment criteria for differentiating atypical AVNRT from AVRT could not be applied to AVRT using slowly conducting concealed septal APs. In the present study, the SA−VA (V2) was obtained in 8 patients with AVRT using slowly conducting APs, but the tachycardia was interrupted by ventricular overdrive pacing in 5 patients. In addition, the SA−VA (V2) in these patients was so variable that it was difficult to differentiate AVNRT from AVRT using slowly conducting APs.
First, this study was a partially retrospective analysis with possible unknown confounders. Second, the number of patients with AVRT that used slowly conducting APs was small and requires further study before any definitive statement can be made. Another study limitation was that we could not comment on the incremental value of additional pacing techniques (i.e., para-Hisian pacing or differential site pacing) because further diagnostic maneuvers were left to the discretion of the operators.
This was a study in which the single V2 was tested for distinguishing AVNRT from AVRT. A SA−VA (V2) of >70 ms using the V2 technique proved to be excellent for differentiation of AVNRT from AVRT using septal or right APs. However, there was overlap between AVNRT and AVRT with left APs. A SA−VA (V2) of >110 ms with a short CI (<65% TCL) effectively differentiated AVNRT from AVRT with left APs. The V2 technique less frequently resulted in tachycardia termination compared with ventricular overdrive pacing. The small number of cases with decremental APs did not allow for definitive conclusions.
COMPETENCY IN MEDICAL KNOWLEDGE: Several maneuvers have been reported for differentiating AVNRT from AVRT, but all of them have some limitations. In addition, many electrophysiologists want to shorten the time to diagnose supraventricular tachycardia and to reduce the number of catheters inserted because of concerns about cost. We introduced a simple maneuver using V2 during supraventricular tachycardia. This technique differentiated between AVNRT and AVRT regardless of AP location. Use of the technique may obviate the need for a CS catheter.
TRANSLATIONAL OUTLOOK: We have shown that this relatively simple technique may be used to quickly diagnose the mechanism of supraventricular tachycardia. More studies are required to assess the valve used in the technique to differentiate patients with AVNRT versus decremental APs.
Dr. Pellegrini has been a consultant for Abbott. Dr. Hsia has been a member of the speakers bureau for Biosense Webster; a member of the Advisory Board for Medtronic; and a consultant for Vytronus. Dr. Scheinman has received honoraria from St. Jude Medical, Medtronic, Biosense Webster, and Biotronik. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
- Abbreviations and Acronyms
- accessory pathway
- atrioventricular nodal re-entrant tachycardia
- atrioventricular re-entrant tachycardia
- coupling interval
- coronary sinus
- post-pacing interval
- right ventricular
- tachycardia cycle length
- stimulus atrial
- Received October 30, 2017.
- Revision received January 16, 2018.
- Accepted January 31, 2018.
- 2018 American College of Cardiology Foundation
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