Author + information
- Received July 9, 2018
- Revision received August 31, 2018
- Accepted September 5, 2018
- Published online January 21, 2019.
- Demosthenes G. Katritsis, MD, PhDa,∗ (, )
- Theodoros Zografos, MDa,
- Konstantinos C. Siontis, MDb,
- George Giannopoulos, MDc,
- Rahul G. Muthalaly, MDd,
- Qiang Liu, MDe,
- Rakesh Latchamsetty, MDb,
- Zoltán Varga, MDf,
- Spyridon Deftereos, MDc,
- Charles Swerdlow, MDe,
- David J. Callans, MDf,
- John M. Miller, MDg,
- Fred Morady, MDb,
- Roy M. John, MDd and
- William G. Stevenson, MDd
- aDepartment of Cardiology, Athens Euroclinic and Hygeia Hospital, Athens, Greece
- bCardiovascular Center, University of Michigan Health System, Ann Arbor, Michigan
- cDepartment of Cardiology, Attikon General Hospital, University of Athens Medical School, Athens, Greece
- dHeart and Vascular Center, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
- eCardiology, University of California, Los Angeles, and Cedars Sinai Medical Center, Los Angeles, California
- fDepartment of Medicine, University of Pennsylvania Health System, Philadelphia, Pennsylvania
- gDepartment of Medicine, Indiana University School of Medicine, Indianapolis, Indiana
- ↵∗Address for correspondence:
Dr. Demosthenes G. Katritsis, Hygeia Hospital, 4 Erythrou Stavrou Street, Athens 15123, Greece.
Objectives This study sought to investigate markers of success following slow pathway ablation for atrioventricular nodal re-entrant tachycardia (AVNRT).
Background Published data are conflicting.
Methods The authors studied 1,007 patients with typical AVNRT and 77 patients with atypical AVNRT.
Results Following ablation, tachycardia was rendered not inducible in all patients. One case of transient (0.09%) and 1 of permanent (0.09%) atrioventricular (AV) block were encountered. At a 3-month follow-up, arrhythmia recurrence was noted in 21 (2.10%) patients in the typical and 3 (3.90%) patients in the atypical group (odds ratio: 0.525; 95% confidence interval [CI]: 0.153 to 1.802; p = 0.298). To predict absence of recurrence in 3 months, the induction of junctional rhythm (95.70% in typical and 96.10% in atypical groups) had sensitivity of 95.9% (95% CI: 94.6% to 97.0%) and specificity of 4.20% (95% CI: 0.11% to 21.10%), while the absence of dual AV nodal conduction post-ablation had sensitivity of 65.2% (95% CI: 62.2% to 68.1%) and specificity of 33.30% (95% CI: 15.60% to 55.30%). Neither junctional rhythm nor residual dual AV nodal pathway conduction were predictive of arrhythmia recurrence by univariate analysis. In long-term follow-up data available for 239 patients, arrhythmia-free survival was not associated with the induction of junctional rhythm or the absence of residual dual AV nodal conduction (log-rank test, p = 0.819 and p = 0.226, respectively).
Conclusions Induction of a junctional rhythm during ablation is a sensitive but not a specific marker of success. Residual dual AV nodal conduction is not predictive of recurrence. Noninducibility of the arrhythmia, usually after ablation-induced junctional rhythm, and despite isoproterenol challenge, is the most credible endpoint for success.
Catheter ablation is the treatment of choice for symptomatic patients with atrioventricular nodal re-entrant tachycardia (AVNRT), but the endpoints of the procedure are still not unequivocally established (1). Seminal studies that proved the efficacy of slow, as opposed to fast, pathway ablation have considered abolition of 1:1 slow pathway conduction as a credible endpoint (2), and junctional ectopy during the application of radiofrequency (RF) energy as a sensitive marker of successful ablation (3). However, induction of a junctional rhythm during RF energy application is not a specific marker of ablation success (3,4), and when fast (average cycle length 363 ms) may indicate impeding atrioventricular (AV) block (5). Persistent slow pathway conduction following ablation has also not been considered a marker of recurrence in most (6–9), but not all (10), recent studies. Residual AV nodal dual conduction as assessed by the induction of echo beats over a range of atrial extrastimulation coupling intervals with a mean of 85 ms, as opposed to a shorter range of 30 ms, has been found predictive of recurrence in a relatively recent survey of 1,419 patients (10). Furthermore, significant gender-related difference in outcome of ablation in patients with AVNRT exist (11), and data on atypical AVNRT are scarce in this respect (10,12).
We have therefore conducted a survey of extensive databases from high-load centers on the efficacy of anatomic slow pathway ablation in patients with typical and atypical AVNRT and sought to identify credible endpoints that indicate a successful long-term outcome.
Databases of participating centers were searched for eligible patients. Data from adult, consecutive patients with documented symptomatic AVNRT undergoing catheter ablation at Athens Euroclinic (Athens, Greece; 2010 to 2015); University of California, Los Angeles, and Cedars Sinai Medical Center (Los Angeles, California; 2010 to 2016); Attikon General Hospital (Athens, Greece; January to June 2017); University of Pennsylvania Health System (Philadelphia, Pennsylvania; January to December 2016); University of Michigan Health System (Ann Arbor, Michigan; 2014 to 2015); Indiana University School of Medicine (Indianapolis, Indiana; 2000 to 2016); and the Brigham and Women’s Hospital (Boston, Massachusetts; 2014 to 2015) were analyzed. Patients with a diagnosis of AVNRT, typical or atypical, subjected to catheter ablation and in whom at least a 3-month follow-up was accomplished, were included in the study. AVNRT was diagnosed by fulfillment of established criteria during detailed atrial and ventricular pacing maneuvers (13). Typical (slow-fast) AVNRT was defined by an atrial-His/His-atrial ratio >1, and His-atrial ratio interval ≤70 ms (14,15). Atypical AVNRT was defined by delayed retrograde atrial activation with His-atrial ratio interval >70 ms. Patients with concomitant arrhythmias such as atrial flutter or fibrillation that required additional ablation were excluded. We also excluded patients with noninducible AVNRT at the onset of the procedure, patients requiring cryoablation, and patients in whom the AVNRT remained inducible (with or without isoproterenol) at the end of the procedure. All patients were studied in the post-absorptive state, under mild sedation, and after all antiarrhythmic agents had been discontinued for more than 5 half-lives. No patient had received amiodarone for the preceding 3 months. The study received approval from our Institutional Review Boards.
Mapping and ablation
Anatomic slow pathway ablation was performed at each center according to standard techniques (16,17). In brief, a conventional 4-mm ablation catheter was positioned at the inferior (posterior) part of the tricuspid annulus until an atrial to ventricular electrogram ratio (A/V ratio) of <1 was recorded, and the atrial electrogram was delayed relatively to the atrial electrogram recorded at the His bundle. Care was taken to keep the ablation catheter below the ostium of the coronary sinus as visualized in the right anterior oblique projection; mapping was not performed at the mid- or anterior septum. When multicomponent signals or separate, low-amplitude potentials were obtained, an RF current, 20 W to 40 W aimed at a temperature of 60°C, was delivered for up to 30 s until a junctional rhythm with 1:1 retrograde ventriculoatrial (VA) conduction was elicited. If a VA conduction was not seen, RF delivery was immediately stopped. Once junctional rhythm with VA conduction was recorded, energy delivery was continued for 10 to 30 s or until cessation of the junctional rhythm. If a junctional rhythm could not be obtained, testing of tachycardia inducibility following ablation was at the operator’s discretion. Residual slow pathway function with single AV nodal echo beats was considered an adequate endpoint, but not if there was more than 1 AV nodal echo. Following ablation, arrhythmia induction with the use of isoproterenol was attempted. If noninducibility of tachycardia could not be accomplished from the right side of the septum, mapping and ablation at the corresponding part of the left septum was undertaken (12,18). The following potential endpoints were considered for analysis: 1) demonstration of RF-induced junctional rhythm conducted to the atria; and 2) post-ablation dual AV nodal conduction.
Continuous, normally distributed variables are presented as mean ± SD and were compared using the Student’s t-test. Non-normally distributed continuous variables are reported as median (interquartile range [IQR]) and were compared with the Wilcoxon test. Categorical data are expressed as frequency and percentage and were compared using the Cochran-Mantel-Haenszel test. Data normality was analyzed using the Shapiro-Wilk test. The association of baseline patients and procedural characteristics, including procedural endpoints, with the 3-month recurrence was tested with univariate logistic regression, stratified according to participating center. Adjusted odds ratio (OR) and 95% confidence interval (CI) according to the Mantel-Haenszel method are reported. We also calculated the sensitivity and specificity (with corresponding 95% CI) of the presence of junctional rhythm and the absence of post-ablation dual AV nodal physiology to predict successful 3-month outcome (no recurrence). The cumulative risk for arrhythmia recurrence was estimated using the Kaplan-Meier procedure and cumulative event rates were compared with the log-rank test. All reported p values were based on 2-sided tests and were compared with a significance level of 5%. Statistical calculations were performed with IBM SPSS Statistics version 23 (IBM Corp., Armonk, New York), and Stata statistical software release 13 (StataCorp, College Station, Texas).
Patients subjected to catheter ablation for typical (n = 1,007) or atypical AVNRT (n = 77) at the Indiana University School of Medicine (n = 503); University of California, Los Angeles, and Cedars Sinai Medical Center (n = 152); Athens Euroclinic (n = 139); Brigham and Women’s Hospital (n = 102); University of Michigan Health System (n = 91); University of Pennsylvania Health System (n = 71); and Attikon General Hospital (n = 26) with data available at the pre-determined 3-month follow-up were included in the analysis. The median age of patients with typical AVNRT was 50 (IQR: 37 to 61) years, and 657 (65.2%) patients were women, while in the atypical group the mean age was 48 (IQR: 32 to 67) years, and 50 (64.9%) patients were women.
AVNRT was inducible, with or without isoproterenol, in all patients at electrophysiology study. All but 13 patients underwent conventional, right-sided ablation at the anatomical area of the slow pathway as described. In 2 patients additional lesions within the coronary sinus ostium were delivered. In 11 patients, a left-sided approach was successfully accomplished following unsuccessful right-sided slow pathway ablation. Ablation characteristics are presented in Table 1. AVNRT was inducible in 943 (87%) patients by atrial extrastimulation or burst pacing. In 93 (8.6%) patients, tachycardia was induced by ventricular pacing, whereas in the remainder (n = 48) tachycardia was induced either by catheter manipulation or spontaneously during isoproterenol infusion. AV nodal dual conduction at electrophysiology study was documented in 871 (80.9%) patients with typical AVNRT and in 65 (84.4%) patients with atypical AVNRT pre-ablation. Post-ablation, residual AV nodal dual conduction was observed in 350 patients with typical and 26 patients with atypical AVNRT. Patients with residual AV nodal dual conduction had significantly higher RF delivery time (6.0 [IQR: 4.0 to 10.25] min vs. 4.9 [IQR: 3.0 to 8.0] min; p = 0.001), and higher, though nonsignificant, fluoroscopy time (16.3 [IQR: 10.9 to 26.0] min vs. 15.7 [IQR: 9.5 to 24.0] min; p = 0.086). Junctional rhythm during RF delivery was recorded in 964 patients with typical AVNRT and 74 patients with atypical AVNRT. Two cases of AV block were encountered. One was transient, whereas the other required permanent pacing.
At 3 months of follow-up arrhythmia recurrence was noted in 21 (2.1%) patients in the typical group and 3 (3.9%) patients in the atypical group (OR: 0.525; 95% CI: 0.153 to 1.802; p = 0.298). No further cases of AV block were noted during follow-up in either the typical or the atypical group.
Predictors of recurrence
In the overall population with noninducible AVRNT at the end of the procedure, the rate of recurrence at 3 months was 2.2% (n = 24). Patients with arrhythmia recurrence were significantly younger compared with those with no recurrence (median 40 years of age vs. median 50 years of age; OR: 0.97; 95% CI: 0.94 to 0.99; p = 0.009). RF current duration was on average longer among patients with recurrence compared with those without recurrence (median 6 min vs. 5 min; p < 0.001). Other characteristics in association with recurrence are shown in Table 2.
Arrhythmia recurrence was observed in 23 patients with junctional rhythm during RF delivery compared with 1 patient with no junctional rhythm during RF delivery. The frequency of arrhythmia recurrence was similar in patients with and those without junctional rhythm during ablation (2.22% vs. 2.27%). The induction of junctional rhythm had sensitivity of 95.9% (95% CI: 94.6% to 97.0%) and specificity of 4.20% (95% CI: 0.11% to 21.10%) to predict successful 3-month outcome (no recurrence). Overall, junctional rhythm was not predictive of arrhythmia recurrence by univariate logistic regression (OR: 0.923; 95% CI: 0.083 to 10.215; p = 0.948).
The frequency of arrhythmia recurrence was similar in patients with and those without residual dual AV nodal conduction following ablation (2.13% vs. 2.27%; p = NS) (Table 3). The absence of dual AV nodal conduction post-ablation had sensitivity of 65.2% (95% CI: 62.2% to 68.1%) and specificity of 33.30% (95% CI: 15.60% to 55.30%) to predict successful 3-month outcome (no recurrence). Overall, residual AV nodal conduction was not predictive of arrhythmia recurrence by univariate logistic regression (OR: 1.028; 95% CI: 0.391 to 2.703; p = 0.956). In patients with junctional rhythm during RF delivery and absence of residual AV nodal dual conduction (n = 677), the rate of arrhythmia recurrence was not significantly different from the rest of the patients (2.36% vs. 1.99%, OR: 1.112; 95% CI: 0.418 to 2.955; p = 0.832).
In 239 patients (214 patients with typical AVNRT), follow-up data were available for a median of 488 days (Figure 1). Three patients had AVNRT recurrence beyond the period of the first 3 months following ablation. The arrhythmia-free survival was not associated with induction of junctional rhythm during ablation (log-rank test, p = 0.819) (Figure 2), or the absence of dual AV nodal conduction post-ablation (log-rank test, p = 0.226) (Figure 3).
Our study is the largest published series of both typical and atypical AVNRT cases subjected to catheter ablation at different centers and by various operators. Results indicate that abolition of inducibility of AVNRT is the relatively most credible marker for slow pathway ablation success. This is true for typical as well as atypical AVNRT, which, in keeping with our previous experience (12), is not a marker of higher ablation failure as reported by other investigators (12). In accordance with previous reports (3,4), we found that induction of a junctional rhythm during RF energy application is not a specific marker of ablation success. In 17 patients, neither a junctional rhythm nor elimination of dual AV nodal conduction could be achieved, but recurrence of arrhythmia was seen in only 1 of them. It should be stated, however, that induction of a junctional rhythm was seen in the majority of patients (approximately 96%) subjected to ablation. Whether our negative findings regarding the nonsignificance of junctional rhythm in predicting success are due to a type II error in the context of the small number of recurrences cannot be deduced from our data. Our data indicate that operators usually test noninducibility of AVNRT after a junctional rhythm has been obtained.
Persistent slow pathway conduction following ablation was also not found to be a marker of recurrence. In the initial report of Jackman et al. (2), the lack of 1:1 retrograde or anterograde slow pathway conduction was a prerequisite for cessation of RF delivery. Our results indicate that this is not necessary anymore. The lack of predictive value of residual slow pathway conduction is in keeping with proposed tachycardia models based on the concept of the inferior nodal extensions as the potential substrate of the slow pathway. Modification of nodal conduction properties seems to be adequate for interruption of the tachycardia circuit without necessarily eradicating the presence of areas of slow conduction that result in AV nodal duality. Connexin staining and genotyping studies have identified the left inferior extension and the AV node itself as areas of low connexin-43 expression and consequently, slow conduction (19,20). On the contrary, the right inferior extension is an area of high connexin-43 expression and, consequently, fast conduction together with the lower nodal bundle, an entity that cannot be identified by conventional histology techniques (19,20). Therefore, it seems reasonable to consider that the left inferior extension probably represents the anatomic substrate of the slow pathway (i.e., the critical isthmus in the AVNRT circuit) (21). Thus, successful right septal ablation may abolish tachycardia inducibility without completely abolishing the slow pathway, presumably due to incomplete destruction of the left inferior extension by right-sided energy applications (Figure 4).
Our data have important clinical implications: 1) this largest multicenter series to date confirms that curative, single-procedure ablation of AVNRT can be achieved in almost 98% of patients, with an extremely low risk of permanent AV block; 2) induction of a junctional rhythm during RF delivery is desirable and should be sought, but it cannot by itself establish success, whereas lack of junctional rhythm induction does not necessitate a recurrence; 3) prolonged procedures aimed at eliminating residual AV nodal duality are unnecessary and potentially harmful by increasing radiation times and, perhaps, the risk of ablation-induced AV block; and 4) achievement of noninducibility of the clinical arrhythmia in the context of induced junctional rhythm during ablation appears to be the most reliable criterion for a successful ablation.
Our results have been derived by high-volume, experienced centers, and, as such, may not be applicable to lower-volume labs. Second, a 3-month-only follow-up was available for the majority of our patients. However, only 3 of 239 patients had AVNRT recurrence beyond the period of the first 3 months following ablation. Usually, in adult patients, recurrences are seen within 3 months following a successful procedure in symptomatic patients with frequent episodes of tachycardia (1–3), and only in the young, ≤18 years of age, a significant number of recurrences may be seen as long as 5 years post-ablation (22). Furthermore, due to the small number of recurrences in the study population, our study has not achieved sufficient statistical power. Therefore, a type II error cannot be precluded. This may be particularly relevant to our results regarding the significance of junctional rhythm induction during ablation.
Among patients with noninducible AVNRT post-ablation, junctional rhythm during radiofrequency current delivery is a sensitive but not a specific marker of ablation success. It is useful, however, to indicate potential noninducibility. The presence of residual post-ablation AV nodal dual pathway physiology is not a marker of recurrence. Abolition of AVNRT inducibility in the presence of isoproterenol challenge is the most reliable marker for ablation success.
COMPETENCY IN MEDICAL KNOWLEDGE: Induction of a junctional rhythm during slow pathway ablation of AVNRT is a sensitive but not a specific marker of ablation success. Residual AV nodal dual conduction should not be sought as a criterion of success. Prolonged procedures aimed at eliminating this behavior are unnecessary and potentially harmful by increasing radiation times and, potentially, the risk of ablation-induced AV block.
TRANSLATIONAL OUTLOOK: Prospective randomized comparisons are needed to delineate the clinical usefulness of a direct left septal approach for AVNRT ablation with the only endpoint being the inability to induce tachycardia following minimal radiofrequency current applications. Additional insights may be required to improve the current high, but imperfect, success rate.
Dr. Zografos has received research support from AstraZeneca. Dr. Muthalaly has received research support from Avant Mutual and Monash Health. Dr. John has received lecture honoraria (modest) for educational programs from Abbott Medical and Medtronic. 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
- atrioventricular nodal re-entrant tachycardia
- confidence interval
- interquartile range
- odds ratio
- Received July 9, 2018.
- Revision received August 31, 2018.
- Accepted September 5, 2018.
- 2019 American College of Cardiology Foundation
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