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Influence of isoproterenol on the accelerated junctional rhythm observed during radiofrequency catheter ablation of atrioventricular nodal slow pathway conduction
Electrophysiology
Influence of isoproterenol on the accelerated junctional rhythm observed during radiofrequency catheter ablation of atrioventricular nodal slow pathway conduction Takehiko Matsushita, MD, PhD, Sung Chun, MD, and Ruey J. Sung, MD Stanford, Calif
Background Accelerated junctional rhythm (AJR) has been considered as a sensitive but rather nonspecific marker of successful radiofrequency (RF) ablation of slow pathway in patients with atrioventricular nodal reentrant tachycardia (AVNRT). However, AJR also occurs commonly during isoproterenol infusion. We therefore investigated the effect of isoproterenol on the significance of AJR while attempting slow pathway ablation.
Methods Forty patients with AVNRT underwent slow pathway ablation. Sixty-nine RF applications accompanied by AJR were observed and were separated into 2 groups: applications performed without (group I, n = 26) and with (group II, n = 43) isoproterenol infusion. The specificity of AJR for successful ablation for each group was calculated.
Results The specificity of AJR in groups I and II was 73% (19/26) and 49% (21/43), respectively (P < .05). There was no significant difference between the groups in the atrial electrogram width, atrial/ventricular electrogram amplitude ratio, the time from application onset to AJR emergence, or AJR cycle length. The catheter-tip temperature at AJR emergence was significantly lower (47°C ± 3°C vs 52°C ± 3°C, P < .001) and the ratio of junctional beats to total heart beats during RF application was significantly greater (46% ± 24% vs 33% ± 18%, P < .05) in group II compared with group I. Conclusions Isoproterenol lowers the threshold of AJR emergence during RF application and thereby lowers the specificity of AJR for successful ablation. Complete washout of isoproterenol may therefore improve the specificity of AJR during RF ablation in patients with AVNRT. (Am Heart J 2001;142:664-8.) The emergence of an accelerated junctional rhythm (AJR) is frequently observed during radiofrequency (RF) energy application to the slow pathway region in catheter ablation therapy for atrioventricular nodal reentrant tachycardia (AVNRT). The AJR during RF application has been postulated to be due to enhanced automaticity of atrioventricular nodal or perinodal tissue in response to thermal effects.1,2 Many studies have reported that the AJR is a sensitive marker of successful modification of slow pathway conduction in the elimination of AVNRT.2-6 However, it has also been reported that the AJR is rather nonspecific because up to 62% of
RF applications producing AJR have been shown to be ineffective in abolishing the inducibility of AVNRT.3,5,6 AJR can also be facilitated by isoproterenol infusion.7,8 Although the mechanism of isoproterenol-induced AJR has also been considered to be the result of an enhanced automaticity, the effects of isoproterenol on the emergence of AJR during RF energy application remain unknown. The purpose of this study was therefore to examine the effects of isoproterenol on the specificity of AJR emerged during RF energy application for successful modification of slow pathway conduction.
Methods From the Cardiac Electrophysiology and Arrhythmia Service, Stanford University Medical Center, Stanford, Calif. Submitted December 21, 2000; accepted June 1, 2001. Reprint requests: Takehiko Matsushita, MD, PhD, Cardiac Electrophysiology and Arrhythmia Service, Stanford University Medical Center, 300 Pasteur Dr, Room H2146, Stanford, CA 94305-5233. E-mail: [email protected] Copyright © 2001 by Mosby, Inc. 0002-8703/2001/$35.00 + 0 4/1/117604 doi:10.1067/mhj.2001.117604
Study population Forty consecutive patients with AVNRT who underwent electrophysiology (EP) study and subsequent RF catheter ablation at Stanford University Medical Center from November 1999 to June 2000 comprised the study population. This consisted of 17 male and 23 female patients ranging in age from 18 to 85 years (55 ± 15 years). All patients had clinically documented episodes of supraventricular tachycardia. Patients provided signed informed consent before enrollment. This study
American Heart Journal Volume 142, Number 4
was approved by the institutional committee on human research.
EP study
Matsushita, Chun, and Sung 665
appeared during RF application, the application was continued for 30 seconds. Atrial pacing with extrastimuli was repeated to assess the effectiveness of the ablation. If the application was not successful, the same series of maneuvers as described above was repeated. A successful ablation was defined as complete elimination of inducible tachycardia without and with intravenous isoproterenol infusion. The presence of residual slow pathway conduction defined by the persistence of discontinuous AV node conduction curves or the presence of a single atrial echo beat was considered successful as long as the AVNRT became no longer inducible after the ablation procedure.
All antiarrhythmic agents were discontinued for at least 5 half-lives before EP study. EP study was performed with the patient in a fasting unsedated state. Standard intracardiac EP techniques were used. Four multipolar electrode catheters (5F or 6F, Daig, Minnetonka, Minn) were positioned with the percutaneous technique: 1 decapolar catheter in the coronary sinus/great cardiac vein with the most proximal electrode pair positioned just inside the ostium and 3 quadripolar catheters in the high right atrium, His bundle region, and right ventricular apex, respectively. Intracardiac electrograms from the coronary sinus, high right atrium, His bundle, and right ventricle, along with surface electrocardiographic leads I, II, and V1, were displayed on a monitor and simultaneously recorded on an optical disk (CardioLab System, Prucka Engineering, Houston, Tex). Pacing protocol consisted of atrial and ventricular incremental overdrive pacing and programmed single and double extrastimuli after 8-beat drive trains at cycle lengths of 600 and 400 milliseconds, respectively. Of all 40 patients, AVNRT was induced in the baseline state with the above pacing protocol in 21 patients. In the remaining 19 patients, isoproterenol (0.5-3.0 µg/min) was required for induction of sustained AVNRT with the same pacing protocol. The electrophysiologic diagnosis of AVNRT was obtained with use of standard criteria.9-11 Dual atrioventricular (AV) node pathway conduction was defined as an increment of 50 milliseconds or more increase in AV node conduction time (AH interval) in response to a 10-millisecond decrement of the atrial premature coupling interval (A1A2) (discontinuous AV node conduction curves).
The RF applications that were accompanied by AJR were separated into 2 groups: applications performed without use of isoproterenol (group I) and those performed with the effects of isoproterenol (group II). Before every RF application, the total atrial electrogram width and the A/V electrogram amplitude ratio at each ablation site were measured. During RF application the following parameters were analyzed: (1) the time from the onset of energy delivery to the first beat of AJR, (2) catheter-tip temperature at the time of AJR occurrence, (3) numbers of total heart beats and junctional beats, and (4) mean AJR cycle length. Mean catheter-tip temperature and mean RF current energy during RF application were also calculated. When more than 1 train of AJR was observed in 1 application, the first AJR train was studied. For group II applications, the heart rate before isoproterenol infusion and that at the onset of RF application along with the last infusion rate of isoproterenol were assessed. If AJR continued after termination of RF energy delivery, it was also included for analysis.
Catheter abation protocol
Statistical analysis
After the diagnosis of AVNRT was confirmed, RF catheter ablation was subsequently performed with a 4-mm tip-deflectable quadripolar catheter (7F, EP Technologies, Sunnyvale, Calif) by use of an anatomic approach.12 The catheter was initially placed at the height of coronary sinus ostium in the posteroseptal region, and RF energy (EPT-1000, EP Technologies) was delivered during sinus rhythm under circuit temperature control (maximum output 30-50 W) to the site with atrial/ventricular (A/V) electrogram amplitude ratio <0.5. If isoproterenol had been infused, it was discontinued and was followed by RF energy delivery to the slow pathway region. The ablation attempt was immediately terminated if an impedance increase or a catheter displacement occurred. In the current study AJR was defined as the occurrence of 3 or more AV junctional premature depolarizations in which atrial activation proceeded initially from the AV junctional region to the high right atrium (low to high sequence) and the QRS complex morphologic features and axis were identical to those seen in sinus beats. If an AJR did not appear within initial 15 seconds of RF energy application, the application was discontinued. The catheter was then moved anteriorly and superiorly toward the His bundle region along the tricuspid annulus but no less than 1.0 cm below the His bundle recording site before another RF application was applied. This series of processes was repeated until an AJR appeared. When an AJR
All data were expressed as mean ± SD. The unpaired t test was used for comparison of continuous variables. The significance of differences was also tested with the nonparametric Mann-Whitney test. Frequency analysis for categorical variables was performed with χ2 analysis. All statistical analyses were performed with Statistica for Windows, version 5.1 (StatSoft, Tulsa, Okla). A value of P < .05 was considered statistically significant.
Statistical analysis
Results EP study and ablation procedure The typical (slow-fast) form of AVNRT was observed in 38 patients, whereas 4 patients had the atypical (fastslow) form. In 2 patients both typical and atypical forms of AVNRT were inducible. In all 40 patients, 211 RF applications were performed in total. The mean number of application per patient was 5.3 ± 5.6 (range 1-16). All patients had successful slow pathway modification without complications. In the 2 patients who had inducible typical and atypical forms of AVNRT, both forms were eliminated with 1 successful RF application. Among all 211 applications, 69 applications were accompanied by AJR during RF energy delivery, of which 40 applications
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666 Matsushita, Chun, and Sung
Figure 1
Table I. Measurements before and during RF application in all RF applications
Heart rate (beats/min) A-wave width (ms) A/V ratio Time to AJR (s) Temperature at AJR emergence (°C) Junctional beats/total heart beats Ratio of junctional beats (%) Cycle length (ms) Mean RF energy (W) Mean temperature (°C)
Histograms of the catheter-tip temperature at the time of AJR emergence. The catheter-tip temperature and the number of applications are shown on the horizontal and vertical axes, respectively. Closed and open bars, Groups I and II, respectively. The temperature ranged from 45°C to 57°C and 42°C to 53°C in groups I and II, respectively. The AJR appeared at less than 50°C in 3 of 26 (12%) in group I compared with 34 of 43 (79%) in group II.
resulted in successful modification of slow pathway conduction and noninducibility of AVNRT.
Specificity of AJR for successful ablation Among 69 applications with AJR, 26 were performed without use of isoproterenol (group I), whereas the remaining 43 were performed under the effects of isoproterenol (group II). For group II applications, the heart rates before isoproterenol infusion and at the onset of RF application immediately after discontinuation of isoproterenol infusion were 73 ± 10 and 92 ± 14 beats/min, respectively (P < .001). The heart rate was increased by 27% ± 12% (range 15%-57%) with the isoproterenol infusion at an infusion rate of 1.8 ± 0.8 µg/min. In group I, 19 of 26 RF applications were successful, whereas 21 of 43 RF applications were successful in group II. Thus the specificity of AJR for successful ablation was 73% and 49% in groups I and II, respectively. The presence of AJR without isoproterenol effects was significantly more specific in predicting successful RF application than the presence of AJR with isoproterenol effects (P < .05).
Measurements The heart rate when the application was performed was significantly higher in group II (P < .001, Table I).
Group I (n = 26)
Group II (n = 43)
74 ± 14* 52 ± 11 0.26 ± 0.12 7.7 ± 3.9 52 ± 3*
92 ± 14 53 ± 16 0.23 ± 0.12 7.3 ± 4.3 47 ± 3
14 ± 9†/44 ± 17
25 ± 20/51 ± 19
33 ± 18‡
46 ± 24
612 ± 175 35 ± 8 49 ± 3
553 ± 105 36 ± 7 47 ± 3
Values are expressed as mean value ± SD. Heart rate, Heart rate at the onset of RF application; A-wave width, total width of the atrial electrogram at the ablation site; A/V ratio, atrial/ventricular electrogram amplitude ratio at the ablation site; time to AJR, the time from the onset of RF application to the first beat of AJR; temperature at AJR emergence, catheter-tip temperature at the time of AJR occurrence; junctional beats, number of junctional beats during RF application; total heart beats, number of total heartbeats during RF application; ratio, the ratio of junctional beats to total heartbeats during RF application; cycle length, mean cycle length of AJR; mean RF energy, mean RF output current energy during RF application; mean temperature, mean catheter-tip temperature during RF application. *P < .001. †P < .01. ‡P < .05.
There were no significant differences in mean catheter-tip temperature or mean RF current energy during RF application between groups I and II (Table I). The time from the onset of RF application to the first beat of AJR in groups I and II was 7.7 ± 3.9 seconds (range 2.0-14.5 seconds) and 7.3 ± 4.3 seconds (range 1.5-14.9 seconds), respectively. There were no significant differences between the 2 groups in the total width of atrial electrogram, A/V electrogram amplitude ratio, or the time from the onset of RF application to the first beat of AJR (Table I). The catheter-tip temperature at the time of AJR appearance was significantly lower and the rate of junctional beats to total heart beats was significantly greater in group II (P < .001 and P < .05, respectively, Table I). There was a trend toward a longer AJR mean cycle length in group I compared with group II, but this did not reach statistical significance (Table I). In 8 of 43 (19%) applications in group II, AJR persisted after cessation of the RF application, whereas there was no persistence of AJR in group I (P < .001). The distribution of the catheter tip temperature at the time of AJR emergence is shown in Figure 1. The temperature ranged from 45°C to 57°C and 42°C to 53°C in groups I and II, respectively. The AJR appeared at less than 50°C in 3 of 26 (12%) in group I compared with 34 of 43 (79%) in group II. Table II summarizes various measurements of suc-
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cessful RF applications in each group. The time from the onset of RF application to the first beat of AJR in groups I and II was 8.2 ± 3.9 seconds (range 2.3-14.4 seconds) and 7.6 ± 4.8 seconds (range 1.5-14.4 seconds), respectively (not significant).
Discussion Major findings The main finding of the current study was that effects of isoproterenol infusion significantly decreased the specificity of AJR for predicting successful modification of slow pathway conduction. The catheter-tip temperature at the time of AJR onset was significantly lower and the ratio of junctional beats to total heart beats during RF application was significantly greater in group II, whereas mean catheter-tip temperature during RF delivery did not significantly differ between groups I and II. These results indicate that isoproterenol lowers the threshold of AJR emergence during RF application. This lowering of the threshold seems to result in the lowering of the specificity. In addition, AJR persisted after cessation of the energy delivery in 19% of applications in group II, whereas there was no persistence of AJR in group I. These findings also support the notion that isoproterenol facilitates the emergence of AJR during RF application. In contrast to the catheter-tip temperature and ratio of junctional beats, the mean cycle length of AJR in group II did not significantly differ from that in group I, although the heart rate at the time of RF energy delivery was significantly higher in group II. Thus isoproterenol, while increasing the sinus rate, may not affect the AJR rate.
Specificity of AJR in predicting successful ablation Although AJR has been reported as a nonspecific marker of successful modification of slow pathway conduction, the specificity of AJR as a marker varied in previous studies. In a recent study, Wagshal et al13 described that the specificity of AJR for successful slow pathway ablation was 95% and that AJR was not a nonspecific regional effect but specific for the slow pathway, whereas our results indicate that the AJR is not as specific even in group I (without isoproterenol) with a rate of 73%. They demonstrated that most of AJR appeared within 4 seconds of the start of RF application. Poret et al14 also reported that, when the AJR appeared within the initial 3 seconds of RF application at the midseptal region, the specificity of AJR for successful slow pathway ablation was 100%. In our study the time from the onset of RF application to the first beat of AJR in successful applications varied widely (1.5-14.4 seconds). Differences in the temperature achieved at the tip of the ablation catheter and the tissue interface of the slow pathway region may partly explain the variation in the results.13
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Table II. Measurements before and during RF application in successful RF applications
Heart rate (beats/min) A-wave width (ms) A/V ratio Time to AJR (s) Temperature (°C) Junctional beats/total heart beats Ratio of junctional beats (%) Cycle length (ms)
Group I (n = 19)
Group II (n = 21)
74 ± 12* 53 ± 11 0.26 ± 0.13 8.2 ± 3.9 52 ± 3* 14 ± 11/43 ± 15
94 ± 16 52 ± 15 0.27 ± 0.15 7.6 ± 4.8 47 ± 3 23 ± 13/49 ± 16
33 ± 20†
45 ± 18
607 ± 167
547 ± 120
Values are expressed as mean value ± SD. For abbreviations, see Table I. *P < .001. †P < .05.
Mechanism of AJR during RF application Emergence of AJR during RF application has been considered to be the result of enhanced automaticity of AV nodal or perinodal tissue in response to thermal effects.1,2,15 The appearance of AJR is also not infrequently seen during isoproterenol infusion, and the mechanism of this isoproterenol-induced AJR has also been considered to be due to enhanced automaticity.7,8 Yu et al6 postulated that AJR during RF application was due to the thermal current conducted through specialized atrionodal fibers to the AV node. However, Boyle et al15 proposed another mechanism that involved multiple automatic foci around slow pathway area with anisotropic conduction to the surrounding atrial tissue. Although isoproterenol-induced AJR can be considered as a result of enhancement of diastolic phase 4 depolarization, the mechanism by which RF provokes AJR at the slow pathway region remains speculative.
Clinical implications Because the sensitivity of AJR for successful slow pathway ablation is extremely high,5,6 it is useful to use the emergence of AJR as a guide for successful RF application during selective ablation of slow pathway conduction. Of note, as shown in the current study, if slow pathway ablation is performed under the effects of isoproterenol, it may result in an increase in total RF application time and hence in total RF energy delivered because of decreased specificity in predicting successful modification of slow pathway conduction. Therefore complete washing out of isoproterenol before slow pathway ablation is performed could minimize unnecessary energy delivery, thus minimizing the potential risk of AV conduction injury.
Study limitations Because this study was a retrospective study, patients were not randomized, and isoproterenol was not used
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668 Matsushita, Chun, and Sung
in group I in which an AVNRT was induced in the baseline state. The fact that isoproterenol is required in some patients and not in others suggests that there might be fundamental differences between the 2 groups. Therefore a randomized prospective study may provide more convincing evidence with regard to our conclusion. Because isoproterenol was discontinued at the time of RF applications in group II, it could be argued that group II did not have many isoproterenol effects. However, in group II the heart rate at the time of RF delivery was significantly higher than at baseline before isoproterenol infusion, with greater than 15% in all patients. Therefore it is unlikely that the effects of isoproterenol had disappeared when the RF energy was delivered.
Conclusions Isoproterenol lowers the threshold of AJR emergence during RF application to the slow pathway region and therefore lowers the specificity of AJR as a marker of successful modification of slow pathway conduction. Complete washing out of isoproterenol will therefore improve the specificity of AJR to serve as a marker of successful slow pathway modification.
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References 1. Thibault B, de Bakker JMT, Hocini M, et al. Origin of heat-induced accelerated junctional rhythm. J Cardiovasc Electrophysiol 1998; 9:631-41. 2. Thakur RK, Klein GJ, Yee R, et al. Junctional tachycardia: a useful marker during radiofrequency ablation for atrioventricular node reentrant tachycardia. J Am Coll Cardiol 1993;22:1706-10. 3. Haissaguerre M, Gaita F, Fischer B, et al. Elimination of atrioventricular nodal reentrant tachycardia using discrete slow potentials to guide application of radiofrequency energy. Circulation 1992;85: 2162-75. 4. Kelly PA, Mann DE, Adler SW, et al. Predictors of successful radiofrequency ablation of extranodal slow pathways. PACE 1994;17: 1143-8. 5. Jentzer JH, Goyal R, Williamson BD, et al. Analysis of junctional
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ectopy during radiofrequency ablation of the slow pathway in patients with atrioventricular nodal reentrant tachycardia. Circulation 1994;90:2820-6. Yu JCL, Lauer MR, Young C, et al. Localization of the origin of the atrioventricular junctional rhythm induced during selective ablation of slow-pathway conduction in patients with atrioventricular node reentrant tachycardia. Am Heart J 1996;131:937-46. Scheinman MM, Gonzalez RP, Cooper MW, et al. Clinical and electrophysiologic features and role of catheter ablation techniques in adult patients with automatic atrioventricular junctional tachycardia. Am J Cardiol 1994;74:565-72. Lee KL, Chun HM, Liem LB, et al. Effect of adenosine and verapamil in catecholamine-induced accelerated atrioventricular junctional rhythm: insights into the underlying mechanism. PACE 1999;22: 866-70. Denes P, Wu D, Dhingra RC, et al. Demonstration of dual AV nodal pathways in patients with paroxysmal supraventricular tachycardia. Circulation 1973;48:549-55. Denes P, Wu D, Dhingra RC, et al. Dual atrioventricular nodal pathways: a common electrophysiologic response. Br Heart J 1975;37: 1069-76. Sung RJ, Styperek JL, Myerburg RJ, et al. Initiation of two distinct forms of atrioventricular nodal reentrant tachycardia during programmed ventricular stimulation in man. Am J Cardiol 1978;42: 404-15. Jazayeri MR, Hempe SL, Sra JS, et al. Selective transcatheter ablation of the fast and slow pathways using radiofrequency energy in patients with atrioventricular nodal reentrant tachycardia. Circulation 1992;85:1318-28. Wagshal AB, Crystal E, Katz A. Patterns of accelerated junctional rhythm during slow pathway catheter ablation for atrioventricular nodal reentrant tachycardia: temperature dependence, prognostic value, and insights into the nature of the slow pathway. J Cardiovasc Electrophysiol 2000;11:244-54. Poret P, Leclercq C, Gras D, et al. Junctional rhythm during slow pathway radiofrequency ablation in patients with atrioventricular nodal reentrant tachycardia: beat-to-beat analysis and its prognostic value in relation to electrophysiologic and anatomic parameters. J Cardiovasc Electrophysiol 2000;11:405-12. Boyle NG, Anselme F, Monahan K, et al. Origin of junctional rhythm during radiofrequency ablation of atrioventricular nodal reentrant tachycardia in patients without structural heart disease. Am J Cardiol 1997;80:575-80.
Influence of isoproterenol on the accelerated junctional rhythm observed during radiofrequency catheter ablation of atrioventricular nodal slow pathway conduction Takehiko Matsushita, MD, PhD, Sung Chun, MD, and Ruey J. Sung, MD Stanford, Calif
Background Accelerated junctional rhythm (AJR) has been considered as a sensitive but rather nonspecific marker of successful radiofrequency (RF) ablation of slow pathway in patients with atrioventricular nodal reentrant tachycardia (AVNRT). However, AJR also occurs commonly during isoproterenol infusion. We therefore investigated the effect of isoproterenol on the significance of AJR while attempting slow pathway ablation.
Methods Forty patients with AVNRT underwent slow pathway ablation. Sixty-nine RF applications accompanied by AJR were observed and were separated into 2 groups: applications performed without (group I, n = 26) and with (group II, n = 43) isoproterenol infusion. The specificity of AJR for successful ablation for each group was calculated.
Results The specificity of AJR in groups I and II was 73% (19/26) and 49% (21/43), respectively (P < .05). There was no significant difference between the groups in the atrial electrogram width, atrial/ventricular electrogram amplitude ratio, the time from application onset to AJR emergence, or AJR cycle length. The catheter-tip temperature at AJR emergence was significantly lower (47°C ± 3°C vs 52°C ± 3°C, P < .001) and the ratio of junctional beats to total heart beats during RF application was significantly greater (46% ± 24% vs 33% ± 18%, P < .05) in group II compared with group I. Conclusions Isoproterenol lowers the threshold of AJR emergence during RF application and thereby lowers the specificity of AJR for successful ablation. Complete washout of isoproterenol may therefore improve the specificity of AJR during RF ablation in patients with AVNRT. (Am Heart J 2001;142:664-8.) The emergence of an accelerated junctional rhythm (AJR) is frequently observed during radiofrequency (RF) energy application to the slow pathway region in catheter ablation therapy for atrioventricular nodal reentrant tachycardia (AVNRT). The AJR during RF application has been postulated to be due to enhanced automaticity of atrioventricular nodal or perinodal tissue in response to thermal effects.1,2 Many studies have reported that the AJR is a sensitive marker of successful modification of slow pathway conduction in the elimination of AVNRT.2-6 However, it has also been reported that the AJR is rather nonspecific because up to 62% of
RF applications producing AJR have been shown to be ineffective in abolishing the inducibility of AVNRT.3,5,6 AJR can also be facilitated by isoproterenol infusion.7,8 Although the mechanism of isoproterenol-induced AJR has also been considered to be the result of an enhanced automaticity, the effects of isoproterenol on the emergence of AJR during RF energy application remain unknown. The purpose of this study was therefore to examine the effects of isoproterenol on the specificity of AJR emerged during RF energy application for successful modification of slow pathway conduction.
Methods From the Cardiac Electrophysiology and Arrhythmia Service, Stanford University Medical Center, Stanford, Calif. Submitted December 21, 2000; accepted June 1, 2001. Reprint requests: Takehiko Matsushita, MD, PhD, Cardiac Electrophysiology and Arrhythmia Service, Stanford University Medical Center, 300 Pasteur Dr, Room H2146, Stanford, CA 94305-5233. E-mail: [email protected] Copyright © 2001 by Mosby, Inc. 0002-8703/2001/$35.00 + 0 4/1/117604 doi:10.1067/mhj.2001.117604
Study population Forty consecutive patients with AVNRT who underwent electrophysiology (EP) study and subsequent RF catheter ablation at Stanford University Medical Center from November 1999 to June 2000 comprised the study population. This consisted of 17 male and 23 female patients ranging in age from 18 to 85 years (55 ± 15 years). All patients had clinically documented episodes of supraventricular tachycardia. Patients provided signed informed consent before enrollment. This study
American Heart Journal Volume 142, Number 4
was approved by the institutional committee on human research.
EP study
Matsushita, Chun, and Sung 665
appeared during RF application, the application was continued for 30 seconds. Atrial pacing with extrastimuli was repeated to assess the effectiveness of the ablation. If the application was not successful, the same series of maneuvers as described above was repeated. A successful ablation was defined as complete elimination of inducible tachycardia without and with intravenous isoproterenol infusion. The presence of residual slow pathway conduction defined by the persistence of discontinuous AV node conduction curves or the presence of a single atrial echo beat was considered successful as long as the AVNRT became no longer inducible after the ablation procedure.
All antiarrhythmic agents were discontinued for at least 5 half-lives before EP study. EP study was performed with the patient in a fasting unsedated state. Standard intracardiac EP techniques were used. Four multipolar electrode catheters (5F or 6F, Daig, Minnetonka, Minn) were positioned with the percutaneous technique: 1 decapolar catheter in the coronary sinus/great cardiac vein with the most proximal electrode pair positioned just inside the ostium and 3 quadripolar catheters in the high right atrium, His bundle region, and right ventricular apex, respectively. Intracardiac electrograms from the coronary sinus, high right atrium, His bundle, and right ventricle, along with surface electrocardiographic leads I, II, and V1, were displayed on a monitor and simultaneously recorded on an optical disk (CardioLab System, Prucka Engineering, Houston, Tex). Pacing protocol consisted of atrial and ventricular incremental overdrive pacing and programmed single and double extrastimuli after 8-beat drive trains at cycle lengths of 600 and 400 milliseconds, respectively. Of all 40 patients, AVNRT was induced in the baseline state with the above pacing protocol in 21 patients. In the remaining 19 patients, isoproterenol (0.5-3.0 µg/min) was required for induction of sustained AVNRT with the same pacing protocol. The electrophysiologic diagnosis of AVNRT was obtained with use of standard criteria.9-11 Dual atrioventricular (AV) node pathway conduction was defined as an increment of 50 milliseconds or more increase in AV node conduction time (AH interval) in response to a 10-millisecond decrement of the atrial premature coupling interval (A1A2) (discontinuous AV node conduction curves).
The RF applications that were accompanied by AJR were separated into 2 groups: applications performed without use of isoproterenol (group I) and those performed with the effects of isoproterenol (group II). Before every RF application, the total atrial electrogram width and the A/V electrogram amplitude ratio at each ablation site were measured. During RF application the following parameters were analyzed: (1) the time from the onset of energy delivery to the first beat of AJR, (2) catheter-tip temperature at the time of AJR occurrence, (3) numbers of total heart beats and junctional beats, and (4) mean AJR cycle length. Mean catheter-tip temperature and mean RF current energy during RF application were also calculated. When more than 1 train of AJR was observed in 1 application, the first AJR train was studied. For group II applications, the heart rate before isoproterenol infusion and that at the onset of RF application along with the last infusion rate of isoproterenol were assessed. If AJR continued after termination of RF energy delivery, it was also included for analysis.
Catheter abation protocol
Statistical analysis
After the diagnosis of AVNRT was confirmed, RF catheter ablation was subsequently performed with a 4-mm tip-deflectable quadripolar catheter (7F, EP Technologies, Sunnyvale, Calif) by use of an anatomic approach.12 The catheter was initially placed at the height of coronary sinus ostium in the posteroseptal region, and RF energy (EPT-1000, EP Technologies) was delivered during sinus rhythm under circuit temperature control (maximum output 30-50 W) to the site with atrial/ventricular (A/V) electrogram amplitude ratio <0.5. If isoproterenol had been infused, it was discontinued and was followed by RF energy delivery to the slow pathway region. The ablation attempt was immediately terminated if an impedance increase or a catheter displacement occurred. In the current study AJR was defined as the occurrence of 3 or more AV junctional premature depolarizations in which atrial activation proceeded initially from the AV junctional region to the high right atrium (low to high sequence) and the QRS complex morphologic features and axis were identical to those seen in sinus beats. If an AJR did not appear within initial 15 seconds of RF energy application, the application was discontinued. The catheter was then moved anteriorly and superiorly toward the His bundle region along the tricuspid annulus but no less than 1.0 cm below the His bundle recording site before another RF application was applied. This series of processes was repeated until an AJR appeared. When an AJR
All data were expressed as mean ± SD. The unpaired t test was used for comparison of continuous variables. The significance of differences was also tested with the nonparametric Mann-Whitney test. Frequency analysis for categorical variables was performed with χ2 analysis. All statistical analyses were performed with Statistica for Windows, version 5.1 (StatSoft, Tulsa, Okla). A value of P < .05 was considered statistically significant.
Statistical analysis
Results EP study and ablation procedure The typical (slow-fast) form of AVNRT was observed in 38 patients, whereas 4 patients had the atypical (fastslow) form. In 2 patients both typical and atypical forms of AVNRT were inducible. In all 40 patients, 211 RF applications were performed in total. The mean number of application per patient was 5.3 ± 5.6 (range 1-16). All patients had successful slow pathway modification without complications. In the 2 patients who had inducible typical and atypical forms of AVNRT, both forms were eliminated with 1 successful RF application. Among all 211 applications, 69 applications were accompanied by AJR during RF energy delivery, of which 40 applications
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666 Matsushita, Chun, and Sung
Figure 1
Table I. Measurements before and during RF application in all RF applications
Heart rate (beats/min) A-wave width (ms) A/V ratio Time to AJR (s) Temperature at AJR emergence (°C) Junctional beats/total heart beats Ratio of junctional beats (%) Cycle length (ms) Mean RF energy (W) Mean temperature (°C)
Histograms of the catheter-tip temperature at the time of AJR emergence. The catheter-tip temperature and the number of applications are shown on the horizontal and vertical axes, respectively. Closed and open bars, Groups I and II, respectively. The temperature ranged from 45°C to 57°C and 42°C to 53°C in groups I and II, respectively. The AJR appeared at less than 50°C in 3 of 26 (12%) in group I compared with 34 of 43 (79%) in group II.
resulted in successful modification of slow pathway conduction and noninducibility of AVNRT.
Specificity of AJR for successful ablation Among 69 applications with AJR, 26 were performed without use of isoproterenol (group I), whereas the remaining 43 were performed under the effects of isoproterenol (group II). For group II applications, the heart rates before isoproterenol infusion and at the onset of RF application immediately after discontinuation of isoproterenol infusion were 73 ± 10 and 92 ± 14 beats/min, respectively (P < .001). The heart rate was increased by 27% ± 12% (range 15%-57%) with the isoproterenol infusion at an infusion rate of 1.8 ± 0.8 µg/min. In group I, 19 of 26 RF applications were successful, whereas 21 of 43 RF applications were successful in group II. Thus the specificity of AJR for successful ablation was 73% and 49% in groups I and II, respectively. The presence of AJR without isoproterenol effects was significantly more specific in predicting successful RF application than the presence of AJR with isoproterenol effects (P < .05).
Measurements The heart rate when the application was performed was significantly higher in group II (P < .001, Table I).
Group I (n = 26)
Group II (n = 43)
74 ± 14* 52 ± 11 0.26 ± 0.12 7.7 ± 3.9 52 ± 3*
92 ± 14 53 ± 16 0.23 ± 0.12 7.3 ± 4.3 47 ± 3
14 ± 9†/44 ± 17
25 ± 20/51 ± 19
33 ± 18‡
46 ± 24
612 ± 175 35 ± 8 49 ± 3
553 ± 105 36 ± 7 47 ± 3
Values are expressed as mean value ± SD. Heart rate, Heart rate at the onset of RF application; A-wave width, total width of the atrial electrogram at the ablation site; A/V ratio, atrial/ventricular electrogram amplitude ratio at the ablation site; time to AJR, the time from the onset of RF application to the first beat of AJR; temperature at AJR emergence, catheter-tip temperature at the time of AJR occurrence; junctional beats, number of junctional beats during RF application; total heart beats, number of total heartbeats during RF application; ratio, the ratio of junctional beats to total heartbeats during RF application; cycle length, mean cycle length of AJR; mean RF energy, mean RF output current energy during RF application; mean temperature, mean catheter-tip temperature during RF application. *P < .001. †P < .01. ‡P < .05.
There were no significant differences in mean catheter-tip temperature or mean RF current energy during RF application between groups I and II (Table I). The time from the onset of RF application to the first beat of AJR in groups I and II was 7.7 ± 3.9 seconds (range 2.0-14.5 seconds) and 7.3 ± 4.3 seconds (range 1.5-14.9 seconds), respectively. There were no significant differences between the 2 groups in the total width of atrial electrogram, A/V electrogram amplitude ratio, or the time from the onset of RF application to the first beat of AJR (Table I). The catheter-tip temperature at the time of AJR appearance was significantly lower and the rate of junctional beats to total heart beats was significantly greater in group II (P < .001 and P < .05, respectively, Table I). There was a trend toward a longer AJR mean cycle length in group I compared with group II, but this did not reach statistical significance (Table I). In 8 of 43 (19%) applications in group II, AJR persisted after cessation of the RF application, whereas there was no persistence of AJR in group I (P < .001). The distribution of the catheter tip temperature at the time of AJR emergence is shown in Figure 1. The temperature ranged from 45°C to 57°C and 42°C to 53°C in groups I and II, respectively. The AJR appeared at less than 50°C in 3 of 26 (12%) in group I compared with 34 of 43 (79%) in group II. Table II summarizes various measurements of suc-
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cessful RF applications in each group. The time from the onset of RF application to the first beat of AJR in groups I and II was 8.2 ± 3.9 seconds (range 2.3-14.4 seconds) and 7.6 ± 4.8 seconds (range 1.5-14.4 seconds), respectively (not significant).
Discussion Major findings The main finding of the current study was that effects of isoproterenol infusion significantly decreased the specificity of AJR for predicting successful modification of slow pathway conduction. The catheter-tip temperature at the time of AJR onset was significantly lower and the ratio of junctional beats to total heart beats during RF application was significantly greater in group II, whereas mean catheter-tip temperature during RF delivery did not significantly differ between groups I and II. These results indicate that isoproterenol lowers the threshold of AJR emergence during RF application. This lowering of the threshold seems to result in the lowering of the specificity. In addition, AJR persisted after cessation of the energy delivery in 19% of applications in group II, whereas there was no persistence of AJR in group I. These findings also support the notion that isoproterenol facilitates the emergence of AJR during RF application. In contrast to the catheter-tip temperature and ratio of junctional beats, the mean cycle length of AJR in group II did not significantly differ from that in group I, although the heart rate at the time of RF energy delivery was significantly higher in group II. Thus isoproterenol, while increasing the sinus rate, may not affect the AJR rate.
Specificity of AJR in predicting successful ablation Although AJR has been reported as a nonspecific marker of successful modification of slow pathway conduction, the specificity of AJR as a marker varied in previous studies. In a recent study, Wagshal et al13 described that the specificity of AJR for successful slow pathway ablation was 95% and that AJR was not a nonspecific regional effect but specific for the slow pathway, whereas our results indicate that the AJR is not as specific even in group I (without isoproterenol) with a rate of 73%. They demonstrated that most of AJR appeared within 4 seconds of the start of RF application. Poret et al14 also reported that, when the AJR appeared within the initial 3 seconds of RF application at the midseptal region, the specificity of AJR for successful slow pathway ablation was 100%. In our study the time from the onset of RF application to the first beat of AJR in successful applications varied widely (1.5-14.4 seconds). Differences in the temperature achieved at the tip of the ablation catheter and the tissue interface of the slow pathway region may partly explain the variation in the results.13
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Table II. Measurements before and during RF application in successful RF applications
Heart rate (beats/min) A-wave width (ms) A/V ratio Time to AJR (s) Temperature (°C) Junctional beats/total heart beats Ratio of junctional beats (%) Cycle length (ms)
Group I (n = 19)
Group II (n = 21)
74 ± 12* 53 ± 11 0.26 ± 0.13 8.2 ± 3.9 52 ± 3* 14 ± 11/43 ± 15
94 ± 16 52 ± 15 0.27 ± 0.15 7.6 ± 4.8 47 ± 3 23 ± 13/49 ± 16
33 ± 20†
45 ± 18
607 ± 167
547 ± 120
Values are expressed as mean value ± SD. For abbreviations, see Table I. *P < .001. †P < .05.
Mechanism of AJR during RF application Emergence of AJR during RF application has been considered to be the result of enhanced automaticity of AV nodal or perinodal tissue in response to thermal effects.1,2,15 The appearance of AJR is also not infrequently seen during isoproterenol infusion, and the mechanism of this isoproterenol-induced AJR has also been considered to be due to enhanced automaticity.7,8 Yu et al6 postulated that AJR during RF application was due to the thermal current conducted through specialized atrionodal fibers to the AV node. However, Boyle et al15 proposed another mechanism that involved multiple automatic foci around slow pathway area with anisotropic conduction to the surrounding atrial tissue. Although isoproterenol-induced AJR can be considered as a result of enhancement of diastolic phase 4 depolarization, the mechanism by which RF provokes AJR at the slow pathway region remains speculative.
Clinical implications Because the sensitivity of AJR for successful slow pathway ablation is extremely high,5,6 it is useful to use the emergence of AJR as a guide for successful RF application during selective ablation of slow pathway conduction. Of note, as shown in the current study, if slow pathway ablation is performed under the effects of isoproterenol, it may result in an increase in total RF application time and hence in total RF energy delivered because of decreased specificity in predicting successful modification of slow pathway conduction. Therefore complete washing out of isoproterenol before slow pathway ablation is performed could minimize unnecessary energy delivery, thus minimizing the potential risk of AV conduction injury.
Study limitations Because this study was a retrospective study, patients were not randomized, and isoproterenol was not used
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668 Matsushita, Chun, and Sung
in group I in which an AVNRT was induced in the baseline state. The fact that isoproterenol is required in some patients and not in others suggests that there might be fundamental differences between the 2 groups. Therefore a randomized prospective study may provide more convincing evidence with regard to our conclusion. Because isoproterenol was discontinued at the time of RF applications in group II, it could be argued that group II did not have many isoproterenol effects. However, in group II the heart rate at the time of RF delivery was significantly higher than at baseline before isoproterenol infusion, with greater than 15% in all patients. Therefore it is unlikely that the effects of isoproterenol had disappeared when the RF energy was delivered.
Conclusions Isoproterenol lowers the threshold of AJR emergence during RF application to the slow pathway region and therefore lowers the specificity of AJR as a marker of successful modification of slow pathway conduction. Complete washing out of isoproterenol will therefore improve the specificity of AJR to serve as a marker of successful slow pathway modification.
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