Author + information
- Received August 30, 2018
- Revision received January 15, 2019
- Accepted January 18, 2019
- Published online April 15, 2019.
- Gwilym M. Morris, BmBCh, PhDa,b,
- Louise Segan, MBBSa,
- Geoff Wong, MBBSa,
- Gareth Wynn, MBChB, MD(Res)a,
- Troy Watts, BSca,
- Patrick Heck, BmBCh, DMa,
- Tomos E. Walters, MBBS, PhDa,
- Ashley Nisbet, MBChB, PhDa,
- Paul Sparks, MBBS, PhDa,
- Joseph B. Morton, MBBS, PhDa,
- Peter M. Kistler, MBBS, PhDc,d,e and
- Jonathan M. Kalman, MBBS, PhDa,c,∗ ()
- aDepartment of Cardiology, Royal Melbourne Hospital, Melbourne, Australia
- bDivision of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom
- cFaculty of Medicine, Dentistry, and Health Sciences, University of Melbourne, Parkville, Victoria, Australia
- dDepartment of Cardiology, The Alfred Hospital, Melbourne, Australia
- eBaker IDI Heart and Diabetes Institute, Melbourne, Australia
- ↵∗Address for correspondence:
Dr. Jonathan M. Kalman, Department of Cardiology, The Royal Melbourne Hospital, Grattan Street, Parkville, Victoria–3050, Australia.
Objectives The goal of this study was to characterize, in detail, focal atrial tachycardia (AT) arising from the crista terminalis to investigate associations with other atrial arrhythmia and to define long-term ablation outcomes.
Background The crista terminalis is known to be the most common site of origin for focal AT, but it is not well characterized.
Methods This study retrospectively identified a total of 548 ablation procedures for AT performed at a single center over a 16-year period, of which 171 were arising from the crista terminalis.
Results Compared with patients with other AT sites of origin, crista terminalis AT patients were older (57.3 vs. 47.3 years), more commonly female (72.9% vs. 59.1%), were more commonly associated with coexistent atrioventricular nodal re-entry tachycardia (17.1% vs. 9.7%), and were more likely to be inducible with programmed stimulation (81.5% vs. 58.9%). There was preferential conduction in the superior-inferior axis along the crista terminalis. Acute ablation success rate was high (92.2%) and improved significantly when three-dimensional mapping was used (98.5%). Recurrence in the first 12 months after a successful ablation was 9.7%. Only 2 patients developed atrial fibrillation over the long-term follow-up of >7 years.
Conclusions This large series characterized the clinical and electrophysiological features and immediate and long-term ablation outcomes for AT originating from the crista terminalis. Features of the tachycardia suggest that age-related localized remodeling of the crista terminalis causes a superficial endocardial zone of conduction slowing leading to re-entry. Ablation outcomes were good, with long-term freedom from atrial arrhythmia.
Focal atrial tachycardia (AT) is an important, although uncommon, cause of supraventricular tachycardia (SVT) accounting for ∼15% of all SVT (1). AT does not occur randomly throughout the atria but cluster at stereotypical anatomic sites. The most common site is the crista terminalis (2), originally reported as a site of origin for focal tachycardia in a series of 18 patients with excellent acute success rates (3). Other studies since then have confirmed that the crista terminalis remains the most common site of origin for focal AT (2). However, since that original publication almost 20 years ago, no studies, to the best of our knowledge, have focused on the clinical and electrophysiological features of this tachycardia or ablation outcomes in a large series with long-term follow-up.
The catheter ablation database at the Royal Melbourne Hospital was examined for patients undergoing ablation of focal AT between the years 1998 and 2014. All patients undergoing ablation of AT were included in this series and classified according to the anatomic site of successful ablation, or earliest mapped activation if ablation was unsuccessful or not attempted. This analysis was a study of patients with focal AT and other mechanisms of SVT; patients with previous ablations for atrial flutter or atrial fibrillation (AF) were excluded. Detailed analysis of the patients with crista terminalis AT was performed, and data for other AT (non–crista terminalis AT) were used as a comparator when required.
Patients underwent a clinically indicated electrophysiology study and radiofrequency ablation after providing written informed consent. Patients were studied in the fasted awake state with minimal sedation. Antiarrhythmic drugs were withheld for at least 5 half-lives before the electrophysiology study.
Catheter positioning and study techniques used for focal AT ablation have been previously described (4), and they comprised the following: 1) coronary sinus catheter (10 pole; 2–5–2 mm interelectrode spacing) positioned fluoroscopically with the proximal electrode bipole at the ostium of the coronary sinus; 2) His bundle electrogram catheter; 3) mapping and ablation catheter (with or without three-dimensional [3D] mapping); and 4) if required by operator preference, crista terminalis catheter (20 pole; 1–3–1 mm interelectrode spacing) positioned vertically along the crista terminalis (Figure 1). AT was diagnosed by using standard electrophysiological criteria (5). Confirmation of the anatomic location on the crista terminalis was made either with intracardiac echocardiogram or from detailed geometry acquired during 3D mapping.
If AT did not occur spontaneously, induction with programmed extra-stimulation (PES) was then attempted; this approach was followed by isoproterenol infusion at 1 to 6 μg/min if PES was unsuccessful alone. Analysis of the mode of initiation (spontaneous, including incessant or requiring PES) and requirement for isoproterenol were performed according to anatomic site. Mapping and ablation of the earliest site of endocardial activity relative to the onset of the surface P wave was performed with a 3.5-mm open irrigated catheter or a 4-mm solid tip catheter. Bipolar intracardiac electrograms were filtered at 30 and 500 Hz, and recorded and stored digitally on a computerized system simultaneously along with the 12-lead surface electrocardiograms. Off-line analysis was performed by using on-screen digital calipers at 200 mm/s speed.
Mapping of AT
Localization of the AT was performed during tachycardia or atrial ectopy by analysis of surface electrocardiogram P-wave morphology, atrial endocardial activation sequence during tachycardia, and point mapping to locate the site of earliest endocardial activation relative to surface P-wave onset (Figure 2). Electrograms were classified as fractionated if they were >50 ms in duration with >3 deviations from baseline, and as a double potential if there were 2 deflections with an isoelectric segment >30 ms in-between. 3D electroanatomic mapping using CARTO (Biosense Webster, Diamond Bar, California) or NavX (St. Jude Medical, St. Paul, Minnesota) was used according to operator preference. This approach evolved over the time course of the study, and in the latter half of the period has been the standard. Conduction velocity was calculated from the electroanatomic map across 5 point pairs starting from the point of earliest activation.
At operator discretion (but in the majority of cases), phrenic nerve testing was performed by pacing from the ablation/mapping catheter at the site of earliest activation at high output (20 mA, pulse width 2 ms); phrenic nerve capture was confirmed by palpation of the diaphragmatic contraction. Temperature feedback control of the power output was used for radiofrequency ablation, aiming to achieve a target temperature of 50°C and a maximum power of 30 W (irrigated) or 50 W (solid tip). Absence of tachycardia or focal atrial ectopy 30 min after ablation, including in response to isoproterenol infusion (up to 6 μg/min) and PES, was defined as acute procedural success.
Post-procedural follow-up was systematic for all patients up to 6 months after the procedure, comprising clinical assessment and a resting 12-lead electrocardiogram (ECG); subsequent follow-up was performed according to clinical need. Additional ECG and Holter monitoring were performed if patients experienced recurrent symptoms during follow-up. Long-term follow-up for the purposes of this research study was not performed for all patients. For crista terminalis AT patients, systematic telephone follow-up was undertaken during the course of this study to assess for recurrence of the presenting symptoms. Patients were also questioned about any diagnosis of AF that had been made after the initial 6-month follow-up.
All variables are expressed as mean ± SD. Continuous variables were analyzed by using an analysis of variance model, and grouped categorical data were analyzed by using the Fisher exact test; p values < 0.05 were considered statistically significant. Pairwise analyses for continuous variables were performed by multiple analyses of variance with Šidák’s multiple comparisons, and a p value <0.05 was considered statistically significant. For categorical data, if the Fisher exact test was statistically significant for the group analysis, multiple pairwise comparisons were performed by using the Fisher exact test, and statistically significant p values were calculated by using the Bonferroni correction.
A total of 548 procedures for AT were identified, of which 171 were arising from the crista terminalis and 377 from all other sites within the atria. The patient characteristics for crista terminalis AT are shown in Table 1.
Compared with the group mean of 59.1%, there was a higher proportion of AT from the crista terminalis in female patients (72.9%; p < 0.0001) and a lower proportion of AT from the right atrial appendage (RAA) in female patients (8.3%; p = 0.0003). There were no other significant differences in sex distribution according to anatomic site (Online Data, Online Table 2).
Compared with the group mean of 47.3 ± 18.4 years, the age at presentation was older for crista terminalis AT (age 57.0 ± 13.5 years; p = 0.0001) and peri-nodal (age 58.7 ± 17.0 years; p = 0.0006) sites and younger for RAA (35.3 ± 16.1 years; p = 0.019) and left atrial appendage (age 29.1 ± 13.2 years; p = 0.025) sites (Table 2). There were no other significant differences in age at presentation according to anatomic site.
Electrophysiological characteristics of crista terminalis AT
Anatomic location and surface ECG characteristics
Data were available regarding the precise anatomic location in 125 cases. The most common site of origin was the mid-third of the crista terminalis (n = 61), followed by the superior (n = 53) then inferior (n = 10) thirds (Figure 3). The superior site and mid-site were significantly more common than an inferior location (p < 0.001), but there was no significant difference in frequency between the superior and mid sites. ECGs were analyzed in 78 cases in which a clear unencumbered P-wave could be identified during tachycardia. The P-wave morphology of true crista terminalis sites was in agreement with previous series (2); the dominant morphology in lead V1 was positive/negative (50 cases) or positive (20 cases). Among those with an apparent superior crista terminalis location, 5 cases originated from the superior and medial extent of the crista terminalis immediately adjacent to the insertion of Bachmann’s bundle. These were analyzed separately (Figure 1, Online Data, Online Table 2, Online Figures 1 and 2). It is noteworthy that this portion of the crista terminalis and the insertion of Bachmann’s bundle are anatomically confluent, and therefore it is not possible to be completely certain of the tissue of origin (6). In this small group, the mean age at presentation was relatively younger at 28.2 ± 4.8 years (Table 2). The P-wave duration at this site was shorter than for true crista terminalis sites (74.7 ± 3.8 vs. 99.6 ± 21.0 ms, respectively; p < 0.05), and the P-wave morphology at this site was highly variable. The P wave in lead V1 was positive in 2 patients, positive/negative in 1 patient, negative in 1 patient, and negative/positive in 1 patient (Online Table 2, Online Figure 2), but in all cases the P-wave was negative in leads aVL and aVR, and positive in the inferior leads (II, III, and aVF).
Mode of initiation
Data were available regarding the mode of initiation in 163 cases of crista terminalis AT and 258 cases of non–crista terminalis AT. There was significant variation in both the mode of initiation and requirement for isoproterenol according to anatomic site of origin (Table 3). For all AT combined, the requirement for PES to initiate the tachycardia was 58.9%. For crista terminalis AT, the tachycardia initiated with PES in 133 (81.5%; p < 0.0001 compared with all AT); 74 of these cases required isoproterenol. Crista terminalis AT exhibited spontaneous onset in the remaining 30 (18.5%), of whom 13 cases required isoproterenol. The 5 episodes of tachycardia originating from the superior and medial extent of the crista terminalis (adjacent to Bachmann’s bundle) all exhibited spontaneous onset of AT. Analysis of mode of onset of AT originating from other atrial sites revealed that spontaneous onset was significantly more common than the group mean for AT originating from the pulmonary veins (91.3%; p < 0.0001), the RAA (84.2%; p < 0.0001), and the left atrial appendage (100%; p < 0.0001). Isoproterenol was required for AT induction in 41.0% of the total cohort; the only significant deviations from the mean were for AT originating from either the pulmonary veins (22.8%; p = 0.0006) or the RAA (10.5%; p = 0.0042).
The mean tachycardia cycle length for all AT was 408 ± 100 ms (range, 182 to 797 ms). The only site with a tachycardia cycle length significantly different from the mean was the RAA (520 ± 130 ms; p = 0.0016). There were no other significant cycle length differences (Table 4).
Acute ablation results for crista terminalis AT and utility of 3D mapping
Of 167 cases, acute procedural success at the first attempt was achieved in 154 (92.2%). The bipolar electrogram at the site of successful ablation was 50 ± 11 ms in duration and was fractionated in 66.3% of cases (Figure 2), with a double potential in 8.3%. Activation time at the site of successful ablation was 50 ± 30 ms ahead of the surface ECG P-wave onset. The mean number of radiofrequency applications was 9 ± 1.2 (radiofrequency duration, 312 ± 40 s), and the mean fluoroscopy time was 18.9 ± 0.8 min. There were no major procedural complications.
An electroanatomic mapping system (CARTO or NavX) was used for the initial procedure in 72 cases (Figures 1, 2, and 4). Mapping was focused on the region of interest, and a mean of 89 ± 37 points were taken. Compared with the use of fluoroscopy alone for catheter guidance, the use of a mapping system increased the chance of single-procedure acute success for crista terminalis AT from 86.6% to 98.5% (p < 0.05) and reduced the fluoroscopy time from 20.4 ± 1.3 min to 16.4 ± 1.2 min (p < 0.05).
Electroanatomic activation maps were used to calculate the conduction velocity away from the point of origin in the superior, inferior, medial (toward the septum), and lateral (toward the pectinate right atrial muscle) directions. Using this approach, preferential conduction was observed in the superior and inferior directions along the long-axis of the crista terminalis (Figures 2 and 4). The mean conduction velocities were as follows: superior, 0.82 ± 0.19 m/s; inferior, 0.90 ± 0.20 m/s; medial, 0.30 ± 0.17 m/s; and lateral, 0.39 ± 0.24 m/s (Figure 4). Conduction velocities in the superior and inferior directions were significantly faster than in the lateral and medial directions (p < 0.001), consistent with known conduction anisotropy in this region (Online Data, Online Table 3).
Association with AF and other atrial arrhythmias
Among patients undergoing ablation for crista terminalis AT, there was a significant association with a second atrial arrhythmia (Table 5). At the index electrophysiology study for crista terminalis AT, atrioventricular nodal re-entry tachycardia (AVNRT) was also diagnosed in 28 patients (17.1%), and this finding was significantly more common than for AT arising from all other sites (9.7%; p < 0.0001). For these patients with AVNRT, the primary arrhythmia was diagnosed as crista terminalis AT by the treating physician based on comparison of procedural data versus the clinical tachycardia (12-lead ECGs and Holter monitor). The precise anatomic localization of the crista terminalis AT in these 28 patients was inferior crista terminalis in 4, mid crista terminalis in 14, and superior crista terminalis in 10 (p = 0.33).
There was no significant difference in the frequency of atrioventricular re-entry tachycardia between the anatomic sites (Table 5). Six patients with crista terminalis AT (3.7%) had at least 1 episode of paroxysmal AF documented before the procedure; this finding was not significantly different from AT from all other sites.
Long-term follow-up of crista terminalis AT
Telephone follow-up was completed for all patients with previous successful ablation for crista terminalis AT. Of the 154 patients with a successful ablation, there were 15 documented recurrences in the first year (9.7%). These patients underwent an additional procedure; in 1 patient, repeat ablation was not attempted because of phrenic nerve capture at the ablation target (the earliest site of activation). All other patients achieved eventual long-term success, although 1 patient required a third ablation to achieve long-term freedom from arrhythmia. The patient requiring 3 ablations was treated early in this series with the initial procedure date within the first 3 years of this dataset. At long-term clinical follow-up, of the 153 patients who received ablation with eventual procedural success, 149 reported complete resolution of their symptoms and no recurrence over the mean follow-up period of 91 months (maximum, 198 months; minimum, 7 months). Another 4 patients reported infrequent palpitations but underwent repeated Holter monitoring and had no documented recurrence of their clinical tachycardia. Two patients had died of unrelated noncardiac conditions.
Two patients with successful ablation and no recurrence of crista terminalis AT were diagnosed with AF 5 and 7 years after the index procedure and commenced treatment with sotalol and flecainide, respectively. No other patients reported a diagnosis of AF at late follow-up, but systematic monitoring was not performed. Three other patients remained on metoprolol for palpitations unrelated to AT, having no SVT documented on Holter monitoring (Table 1).
To the best of our knowledge, electrophysiological characteristics and acute and long-term outcomes for tachycardias originating from the crista terminalis have not been described in a large series with long-term follow-up. Our study showed that compared with patients with other AT sites of origin, crista terminalis AT patients were older, more commonly female, were more commonly associated with coexistent AVNRT, and were more likely to be inducible with programmed stimulation. The acute ablation success rate was high and improved significantly when 3D mapping was used. Recurrence in the first 12 months after a successful ablation was uncommon. In long-term follow-up of >7 years, although systematic monitoring was not performed, only 2 patients had received a clinical diagnosis of AF (Central Illustration).
Mechanism of crista terminalis AT
In the series presented here, the crista terminalis was the most common site of AT, accounting for 31% of all AT, similar to previous studies (2). The reason for this finding may be the unique electrophysiological properties of the crista terminalis; the normal crista terminalis is functionally distinct from the surrounding atrial pectinate muscle. For example, the crista terminalis has high levels of collagen with poor cell-to-cell coupling, expresses low conductance connexions, and displays cellular automaticity (6,7). The observed automaticity (7) and anisotropy (8) at the crista terminalis may partly explain the propensity for atrial arrhythmias to originate from this location. In keeping with this hypothesis, an experimental model of AT using inhibition of the atrial ganglionated plexi induced AT at sites similar to those reported clinically (9).
Although the crista terminalis has these distinct properties, the development of clinically relevant AT would require an additional pathological process. Our data showed that crista terminalis AT has some unique properties compared with AT from other sites, providing insight into the mechanisms and pathology. A high proportion of crista terminalis AT required PES for initiation (81.5%), indicating micro re-entry as the probable dominant arrhythmia mechanism. In addition, the mean age of patients with crista terminalis AT was ∼10 years older than patients with AT from other sites (57.0 ± 13.5 years vs. 47.3 ± 18.4 years, respectively), suggesting that crista terminalis remodeling is important in the generation of the arrhythmia substrate. With advancing age, preferential remodeling at the crista terminalis has been previously reported with an increase in anatomically determined functional conduction delay at this site (10). In further support of the role of re-entry as the main arrhythmia mechanism, our data show significant conduction anisotropy at the crista terminalis, with preferential conduction in the superior-inferior axis and slowed conduction in the lateral-medial axis. There was a significant excess of female patients with crista terminalis AT (72.9%) that was not seen in AT from other sites (50.8%). AT as a mechanism of SVT has previously been reported to be more common in female patients (1), and our data suggest that this difference is driven by the sex difference of crista terminalis AT. The reasons for the observed female propensity are not clear; among patients without crista terminalis AT, there is no evidence for sex differences in atrial electrophysiology at any site within the right atrium (11).
Relationship with AF and other arrhythmias
Although crista terminalis foci have been implicated in the initiation of AF (12–14), in our series of 171 patients who presented with a clinical rhythm of focal AT, only 2 developed AF in 7 years of follow-up, suggesting that crista terminalis AT does not seem to be a risk factor for late development of AF. Patients with a previous ablation for AF were excluded from the analysis. This implies that the age-related remodeling that leads to the development of crista terminalis AT is likely a local rather than a diffuse process in these patients. Although systematic monitoring for asymptomatic AF was not performed, we believe that the low rate of symptomatic AF is striking and generally indicates a low likelihood that crista terminalis AT is the forerunner of AF.
The prevalence of a second atrial arrhythmia treated or diagnosed at the index procedure for crista terminalis AT was 31%, and it may be that the AT is acting as an initiating trigger for the second atrial arrhythmia for which there is a coincident underlying substrate. However, there was a significant association with AVNRT (17.1%) not seen with AT from other sites. This finding raises the possibility in these cases that remodeling of the crista terminalis has both caused crista terminalis AT and modified the substrate for AVNRT. The reason for this outcome is not clear; however, it may be hypothesized that remodeling of the inferior portion of the crista terminalis might affect a portion of the slow pathway or alter the electrical coupling of the atrium to the slow pathway, thus increasing the probability of AVNRT induction. Anatomically, the crista terminalis extends into the Eustachian ridge, across the orifice of the inferior vena cava toward the coronary sinus ostium near the proximal segment of the slow pathway (6). In this region, there is evidence of “nodal” type tissue (i.e., similar to the crista terminalis) (15–17), and thus a theoretical possibility exists that remodeling of the crista terminalis could extend to this region near the slow pathway; this theory is unproven, however.
Overall acute ablation success was high (92.2%); with the use of 3D mapping later in the series, it improved further to 98.5%. The crista terminalis is a muscle bundle up to 10 mm thick (6), which is at the limit of lesion depth formation by radiofrequency ablation (18). Furthermore, the crista terminalis is frequently penetrated by the sinus node arterial (6), which, if present, would have a cooling effect, reducing the effectiveness of ablation. Under these conditions, the high acute success rate for ablation of crista terminalis AT suggests an endocardial critical zone of superficial conduction slowing, rendering the tachycardia very sensitive to ablation. The bipolar electrogram at the site of successful ablation was predominantly fractionated (63%), further suggesting the presence of conduction slowing.
Data collection was retrospective. Detection of atrial fibrillation was based on symptoms, therefore asymptomatic AF may have been missed. Long-term follow up of AT from other sites was not undertaken for comparison.
COMPETENCY IN MEDICAL KNOWLEDGE: The crista terminalis is the most common site for focal AT and thus will be frequently encountered by cardiologists and electrophysiologists. These results show that it is a disease of age-related localized remodeling at the crista terminalis, and therefore treatment by ablation should be considered because it has excellent long-term success rates, low complication rates, and little evidence of progression to other atrial arrhythmias. Intriguingly, there was an association with AVNRT; thus, crista terminalis AT should be considered as a differential diagnosis when patients present with palpitations after an ablation for AVNRT.
TRANSLATIONAL OUTLOOK: Although the crista terminalis is understood to be an area with unique electrophysiological properties (e.g., compared with atrial muscle, it expresses low conductance gap junction proteins and higher levels of HCN channels conferring automaticity), the additional remodeling required to cause clinical AT is unknown. Further detailed investigation of the changes occurring with aging in this region may help to reveal the mechanism.
The crista terminalis is the most common site of origin for AT; this arrhythmia is more common in women, is more likely to require PES for initiation, and presents later in life than other AT, suggesting a role for re-entry and age-related remodeling in its pathogenesis. However, the remodeling seems to be localized because progression to AF after successful treatment was rare. Coexisting AVNRT was common in this group, and radiofrequency ablation had a high success rate with low complications and good long-term freedom from atrial arrhythmia.
Dr. Morris is supported by a British Heart Foundation Intermediate Fellowship. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. William Stevenson, MD, served as Guest Editor for this paper.
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
- atrial fibrillation
- atrial tachycardia
- atrioventricular nodal re-entry tachycardia
- programmed extra stimulation
- right atrial appendage
- supraventricular tachycardia
- Received August 30, 2018.
- Revision received January 15, 2019.
- Accepted January 18, 2019.
- 2019 American College of Cardiology Foundation
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