Atrial Tachycardia Arising from the Crista Terminalis, Detailed Electrophysiological Features and Long-Term Ablation Outcomes DOI: 10.1016/J.Jacep.2019.01.014

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Atrial Tachycardia Arising From the Crista Terminalis, Detailed Electrophysiological Features and Long-Term Ablation Outcomes DOI: 10.1016/j.jacep.2019.01.014

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Citation for published version (APA): Morris, G. M., Segan, L., Wong, G., Wynn, G., Watts, T., Heck, P., Walters, T. E., Nisbet, A., Sparks, P., Morton, J. B., Kistler, P. M., & Kalman, J. M. (2019). Atrial Tachycardia Arising From the Crista Terminalis, Detailed Electrophysiological Features and Long-Term Ablation Outcomes. JACC: Clinical Electrophysiology, 5(4), 448-458. https://doi.org/10.1016/j.jacep.2019.01.014 Published in: JACC: Clinical Electrophysiology

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Download date:09. Oct. 2021 JACC: CLINICAL ELECTROPHYSIOLOGY VOL. - ,NO.- ,2019

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AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION

Atrial Tachycardia Arising From the Crista Terminalis, Detailed Electrophysiological Features and Long-Term Ablation Outcomes

a,b a a a Gwilym M. Morris, BMBCH,PHD, Louise Segan, MBBS, Geoff Wong, MBBS, Gareth Wynn, MBCHB, MD(RES), a a a a Troy Watts, BSC, Patrick Heck, BMBCH, DM, Tomos E. Walters, MBBS, PHD, Ashley Nisbet, MBCHB, PHD, a a c,d,e Paul Sparks, MBBS, PHD, Joseph B. Morton, MBBS, PHD, Peter M. Kistler, MBBS, PHD, a,c Jonathan M. Kalman, MBBS, PHD

ABSTRACT

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%). Recur- rence 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. (J Am Coll Cardiol EP 2019;- :-–-) © 2019 Published by Elsevier on behalf of the American College of Cardiology Foundation.

ocal atrial tachycardia (AT) is an important, the atria but cluster at stereotypical anatomic sites. F although uncommon, cause of supraventricu- The most common site is the crista terminalis (2), lar tachycardia (SVT) accounting for w15% of originally reported as a site of origin for focal tachy- all SVT (1). AT does not occur randomly throughout cardia in a series of 18 patients with excellent acute

From the 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; and the eBaker IDI Heart and Diabetes Institute, Melbourne, Australia. 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 Steveson, 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’ in- stitutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.

Manuscript received August 30, 2018; revised manuscript received January 15, 2019, accepted January 18, 2019.

ISSN 2405-500X/$36.00 https://doi.org/10.1016/j.jacep.2019.01.014

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ABBREVIATIONS success rates (3).Otherstudiessincethen attempted; this approach was followed by isoproter- AND ACRONYMS have confirmed that the crista terminalis re- enol infusion at 1 to 6 mg/min if PES was unsuccessful mains the most common site of origin for alone. Analysis of the mode of initiation (sponta- 3D = three-dimensional focal AT (2). However, since that original neous, including incessant or requiring PES) and AF = atrial fibrillation publication almost 20 years ago, no studies, requirement for isoproterenol were performed ac- AT = atrial tachycardia to the best of our knowledge, have focused cording to anatomic site. Mapping and ablation of the AVNRT = atrioventricular on the clinical and electrophysiological fea- earliest site of endocardial activity relative to the nodal re-entry tachycardia tures of this tachycardia or ablation outcomes onset of the surface P wave was performed with a 3.5- ECG = electrocardiogram in a large series with long-term follow-up. mm open irrigated catheter or a 4-mm solid tip PES = programmed extra catheter. Bipolar intracardiac electrograms were stimulation METHODS filtered at 30 and 500 Hz, and recorded and stored RAA = right atrial appendage digitally on a computerized system simultaneously SVT = supraventricular STUDY POPULATION. The catheter ablation along with the 12-lead surface electrocardiograms. tachycardia database at the Royal Melbourne Hospital Off-line analysis was performed by using on-screen was examined for patients undergoing ablation of digital calipers at 200 mm/s speed. focal AT between the years 1998 and 2014. All pa- MAPPING OF AT. Localization of the AT was per- tients undergoing ablation of AT were included in this formed during tachycardia or atrial ectopy by analysis series and classified according to the anatomic site of of surface electrocardiogram P-wave morphology, successful ablation, or earliest mapped activation if atrial endocardial activation sequence during tachy- ablation was unsuccessful or not attempted. This cardia, and point mapping to locate the site of earliest analysis was a study of patients with focal AT and endocardial activation relative to surface P-wave other mechanisms of SVT; patients with previous onset (Figure 2). Electrograms were classified as ablations for atrial flutteroratrialfibrillation (AF) fractionated if they were >50 ms in duration with >3 were excluded. Detailed analysis of the patients with deviations from baseline, and as a double potential if crista terminalis AT was performed, and data for there were 2 deflections with an isoelectric segment other AT (non–crista terminalis AT) were used as a >30 ms in-between. 3D electroanatomic mapping comparator when required. using CARTO (Biosense Webster, Diamond Bar, Cali- ELECTROPHYSIOLOGICAL STUDY. Patients under- fornia) or NavX (St. Jude Medical, St. Paul, Minne- went a clinically indicated electrophysiology study sota) was used according to operator preference. This and radiofrequency ablation after providing written approach evolved over the time course of the study, informed consent. Patients were studied in the fasted and in the latter half of the period has been the awake state with minimal sedation. Antiarrhythmic standard. Conduction velocity was calculated from drugs were withheld for at least 5 half-lives before the the electroanatomic map across 5 point pairs starting electrophysiology study. from the point of earliest activation. Catheter positioning and study techniques used for RADIOFREQUENCY ABLATION. At operator discre- focal AT ablation have been previously described (4), tion (but in the majority of cases), phrenic nerve and they comprised the following: 1) coronary sinus testing was performed by pacing from the ablation/ catheter (10 pole; 2–5–2 mm interelectrode spacing) mapping catheter at the site of earliest activation at positioned fluoroscopically with the proximal elec- high output (20 mA, pulse width 2 ms); phrenic nerve trode bipole at the ostium of the coronary sinus; 2) capture was confirmed by palpation of the diaphrag- His bundle electrogram catheter; 3) mapping and matic contraction. Temperature feedback control of ablation catheter (with or without three-dimensional the power output was used for radiofrequency abla- [3D] mapping); and 4) if required by operator prefer- tion, aiming to achieve a target temperature of 50C ence, crista terminalis catheter (20 pole; 1–3–1mm and a maximum power of 30 W (irrigated) or 50 W interelectrode spacing) positioned vertically along (solid tip). Absence of tachycardia or focal atrial the crista terminalis (Figure 1). AT was diagnosed by ectopy 30 min after ablation, including in response to using standard electrophysiological criteria (5). isoproterenol infusion (up to 6 mg/min) and PES, was Confirmation of the anatomic location on the crista defined as acute procedural success. terminalis was made either with intracardiac echo- cardiogram or from detailed geometry acquired dur- PATIENT FOLLOW-UP. Post-procedural follow-up ing 3D mapping. was systematic for all patients up to 6 months after If AT did not occur spontaneously, induction the procedure, comprising clinical assessment and a with programmed extra-stimulation (PES) was then resting 12-lead electrocardiogram (ECG); subsequent

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FIGURE 1 Focal Atrial Tachycardia Arising From the Insertion of Bachmann’s Bundle FPO = print & web 4C

(A) Intracardiac electrograms recorded from catheters in the positions shown in panel C. The site of successful ablation (ABLd) is 35 ms ahead of the earliest signal on the superior pole of the crista terminalis catheter. (B) CARTO activation map in left anterior oblique (LAO) projection showing the site of earliest activation (shown as red) medial to the superior aspect of the crista terminalis. The site of successful ablation is shown by the red dot. Activation times are shown relative to a stable intracardiac electrogram in the coronary sinus used as a ﬁducial point. RA ¼ right atrium; LA ¼ left atrium. (C) Intracardiac catheter positions shown by ﬂuoroscopy in LAO and right anterior oblique (RAO) pro- jections. The distal bipole of the ablation catheter (*) is at the site of earliest activation and successful ablation. The diagnostic catheters are crista terminalis (CT), His, and coronary sinus (CS).

follow-up was performed according to clinical need. value < 0.05 was considered statistically significant. Additional ECG and Holter monitoring were per- For categorical data, if the Fisher exact test was sta- formed if patients experienced recurrent symptoms tistically significant for the group analysis, multiple during follow-up. Long-term follow-up for the pur- pairwise comparisons were performed by using the posesofthisresearchstudywasnotperformedforall Fisher exact test, and statistically significant p values patients. For crista terminalis AT patients, systematic were calculated by using the Bonferroni correction. telephone follow-up was undertaken during the course of this study to assess for recurrence of the RESULTS presenting symptoms. Patients were also questioned about any diagnosis of AF that had been made after PATIENT CHARACTERISTICS. Atotalof548proced- the initial 6-month follow-up. ures for AT were identified, of which 171 were arising STATISTICAL ANALYSIS. All variables are expressed from the crista terminalis and 377 from all other sites as mean SD. Continuous variables were analyzed by within the atria. The patient characteristics for crista using an analysis of variance model, and grouped terminalis AT are shown in Table 1. categorical data were analyzed by using the Fisher Sex. Compared with the group mean of 59.1%, there exact test; p values <0.05 were considered statisti- was a higher proportion of AT from the crista termi- cally significant. Pairwise analyses for continuous nalis in female patients (72.9%; p < 0.0001) and a variables were performed by multiple analyses of lower proportion of AT from the right atrial appendage variance with Sidák’s multiple comparisons, and a p (RAA) in female patients (8.3%; p ¼ 0.0003).

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FIGURE 2 Representative Example of an Atrial Tachycardia Arising From the Junction of the Middle and Lower Thirds of the Crista Terminalis FPO = print & web 4C

(A) The tachycardia has a cycle length of 444 ms. P-wave morphology is displayed during a transient period of atrioventricular block. (Bi) The intracardiac electrograms show that the point of earliest activation (red arrow) is –145 ms relative to a fiducial point taken at a stable atrial electrogram in the CS and is fractionated. (Bii) CARTO map showing local activation time (LAT) in RAO 57 view showing point of earliest activation in red. (Biii) LAO 60 showing latest activation in the CS in purple. (C) Propagation map showing activation in steps of 4 to 6 ms. The first 4 panels are in RAO 57 view to allow view of the posterior aspect of the RA and the point of first activation; the final 2 panels are shallow RAO (23) to show activation of the interatrial septum and CS. IVC ¼ inferior vena cava; RAA ¼ right atrial appendage; SVC ¼ superior vena cava; other abbreviations as in Figure 1.

There were no other significant differences in sex ELECTROPHYSIOLOGICAL CHARACTERISTICS OF distribution according to anatomic site (Online Data, CRISTA TERMINALIS AT. Anatomic location and Online Table 1). surface ECG characteristics. Data were available Age. Comparedwiththegroupmeanof47.3 18.4 regarding the precise anatomic location in 125 cases. years, the age at presentation was older for crista Themostcommonsiteoforiginwasthemid-thirdof terminalis AT (57.0 13.5 years; p ¼ 0.0001) and peri- the crista terminalis (n ¼ 61), followed by the superior nodal (58.7 17.0 years; p ¼ 0.0006) sites and (n ¼ 53) then inferior (n ¼ 10) thirds (Figure 3). The younger for RAA (35.3 16.1 years; p ¼ 0.019) and left superior site and mid-site were significantly more atrial appendage (29.1 13.2 years; p ¼ 0.025) sites common than an inferior location (p < 0.001), but (Table 2). There were no other significant differences there was no significant difference in frequency be- in age at presentation according to anatomic site. tween the superior and mid sites. ECGs were analyzed

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TABLE 1 Crista Terminalis Atrial Tachycardia Descriptive Data: FIGURE 3 Anatomic Distribution of the Site of Successful Ablation on the Crista Procedural Characteristics and Outcomes Terminalis

Age at diagnosis, mean SEM, yrs 56.9 1.5 Female 127 (74%) Follow-up duration, mean SEM, yrs 7.63 0.35 Pre-existing structural heart disease* 5.2% Mean no. of ablation procedures 1.2 per patient FPO

Self-reported improvement in 93.1% = symptoms Post-procedural CCS-SAF score 86.0%/12.2%/1.8%/0%/ of 0/1/2/3/4 0%

Long-term antiarrhythmic medication† 2.9% print & web 4C

*Atrial septal defect, n ¼ 4; tetralogy of Fallot, n ¼ 3; 2 dilated cardiomyopathy, n ¼ 2; aortic stenosis, n ¼ 2; aortic valve replacement, n ¼ 1; bicuspid aortic valve, n ¼ 1; hypertrophic cardiomyopathy, n ¼ 1; mitral valve replacement, n ¼ 1; pericardiectomy, n ¼ 1; and ventricular septal defect, n ¼ 1. †Metoprolol, n ¼ 3; ﬂecainide, n ¼ 1; and sotalol, n ¼ 1. CCS-SAF ¼ Canadian Cardiovascular Society Severity of Atrial Fibrillation.

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, (A) Overall, the most common site was the mid crista terminalis (61 cases), then the su- Online Figures 1 and 2). It is noteworthy that this perior (53 cases), then inferior (10 cases). There was 1 case of multifocal atrial tachycardia arising from >1 site on the crista terminalis. (B) Representative illustration of the distri- portion of the crista terminalis and the insertion of bution of crista terminalis atrial tachycardia. Abbreviations as in Figures 1 and 2. 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 was shorter than for true crista terminalis sites (74.7 age at presentation was relatively younger at 28.2 3.8 vs. 99.6 21.0 ms, respectively; p < 0.05), and the 4.8 years (Table 2). The P-wave duration at this site P-wave morphology at this site was highly variable.

The P wave in lead V1 was positive in 2 patients,

TABLE 2 Age According to Anatomic Site of Origin positive/negative in 1 patient, negative in 1 patient, and negative/positive in 1 patient (Online Table 2, Age, yrs (Mean SD) Significance* Online Figure 2), but in all cases the P wave was All atrial tachycardia 47.3 18.4 NA negative in leads aVL and aVR, and positive in the Crista terminalis 57.0 13.5 0.0001† Tricuspid annulus 48.9 17.6 0.99 (NS) inferior leads (II, III, and aVF). Coronary sinus 44.3 21.6 0.92 (NS) Mode of initiation. Data were available regarding Peri-nodal 58.7 17.0 0.0006† themodeofinitiationin163casesofcristaterminalis Mitral annulus 54.6 16.0 0.30 (NS) AT and 258 cases of non–crista terminalis AT. There Bachmann’s bundle 28.2 4.8 0.089 (NS) was significant variation in both the mode of initia- Septal 54.1 13.1 0.33 (NS) tion and requirement for isoproterenol according to Pulmonary veins 42.1 16.2 0.14 (NS) anatomic site of origin (Table 3). For all AT combined, Right atrial appendage 35.3 16.1 0.019† Left atrial appendage 29.1 13.2 0.025† the requirement for PES to initiate the tachycardia was 58.9%. For crista terminalis AT, the tachycardia *p value, with multiple analyses of variance versus all atrial tachycardia groups. initiated with PES in 133 (81.5%; p < 0.0001 compared †Statistically significant. NA ¼ not applicable. with all AT); 74 of these cases required isoproterenol. Crista terminalis AT exhibited spontaneous onset in

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TABLE 3 Tachycardia Initiation

Total % Initiation Total % Signiﬁcance for Overall % With PES (% of These Spontaneous Initiation Mode of initiation; Requirement for Signiﬁcance for Requiring Additional (% of These Requiring PES Versus Isoproterenol Overall Isoproterenol Isoproterenol) Additional Isoproterenol) Spontaneous* for Initiation Requirement for Initiation* Group analysis of all AT by the 58.9 (23.6) 41.1 (19.5) <0.001† 41.0 0.0163† Fisher exact test All non–crista terminalis 44.2 (45.6) 55.8 (23.6) <0.0001† 47.9 0.113 (NS) Crista terminalis 81.5 (55.6) 18.5 (43.3) <0.0001† 55.2 0.113 (NS) Tricuspid annulus 57.1 (52.8) 42.9 (22.2) 0.784 (NS) 39.7 0.891 (NS) Coronary sinus 58.5 (52.7) 41.5 (30.7) 0.917 (NS) 43.6 0.640 (NS) Peri-nodal 77.4 (29.1) 22.6 (22.2) 0.037 (NS) 29.0 0.188 (NS) Mitral annulus 55.6 (58.3) 44.4 (50.0) 0.631 (NS) 55.5 0.220 (NS) Bachmann’s bundle 60.0 (33.3) 40.0 (0) 0.999 (NS) 20.0 0.654 (NS) Septal 61.1 (9.1) 38.9 (28.6) 0.851 (NS) 16.7 0.047 (NS) Pulmonary veins 8.7 (40.0) 91.3 (21.2) 0.0001† 22.8 0.0006† Right atrial appendage 15.8 (33.3) 84.2 (6.3) 0.0001† 10.5 0.0042† Left atrial appendage 0 (0) 100 (10) 0.0001† 10.0 0.0528 (NS)

Values are %. *p value (Fisher exact test, p < 0.05 significance for group analysis; p value for significance for pairwise comparisons by Bonferroni correction, p < 0.005). †Statistically significant. AT ¼ atrial tachycardia; PES ¼ programmed electrical stimulation.

the remaining 30 (18.5%), of whom 13 cases required more common than the group mean for AT originating isoproterenol. The 5 episodes of tachycardia origi- from the pulmonary veins (91.3%; p < 0.0001), the nating from the superior and medial extent of the RAA (84.2%; p < 0.0001), and the left atrial crista terminalis (adjacent to Bachmann’s bundle) all appendage (100%; p < 0.0001). Isoproterenol was exhibited spontaneous onset of AT. Analysis of mode required for AT induction in 41.0% of the total cohort; of onset of AT originating from other atrial sites the only significant deviations from the mean were revealed that spontaneous onset was significantly for AT originating from either the pulmonary veins (22.8%; p ¼ 0.0006) or the RAA (10.5%; p ¼ 0.0042). The mean tachycardia cycle length for all AT was TABLE 4 Tachycardia Cycle Length 408 100 ms (range, 182 to 797 ms). The only site Cycle Length, ms with a tachycardia cycle length significantly different (Mean SD) p Value fromthemeanwastheRAA(520 130 ms; p ¼ All AT 408 100 NA 0.0016). There were no other significant cycle length Crista terminalis 412 77 0.999 differences (Table 4). All non–crista terminalis 405 113 0.999 Tricuspid annulus 398 92 0.980 ACUTE ABLATION RESULTS FOR CRISTA TERMI- Coronary sinus 369 110 0.400 NALIS AT AND UTILITY OF 3D MAPPING. Of 167 Peri-nodal 403 98 0.999 cases, acute procedural success at the first attempt Mitral annulus 439 162 0.991 was achieved in 154 (92.2%). The bipolar electrogram Bachmann’s bundle 391 50 0.999 Septal 428 124 0.992 at the site of successful ablation was 50 11 ms in Pulmonary veins 366 91 0.139 duration and was fractionated in 66.3% of cases Right atrial appendage 520 130 0.0016* (Figure 2), with a double potential in 8.3%. Activation Left atrial appendage 507 73 0.078 timeatthesiteofsuccessfulablationwas50 30 ms Crista terminalis, female 389 71 0.090 (female vs. male) ahead of the surface ECG P-wave onset. The mean Crista terminalis, male 412 95 0.090 (female vs. male) number of radiofrequency applications was 9 1.2 Crista terminalis, PES 416 75 0.672 (PES vs. spontaneous) (radiofrequency duration, 312 40 s), and the mean Crista terminalis, spontaneous 404 74 0.672 (PES vs. spontaneous) fluoroscopy time was 18.9 0.8 min. There were no Crista terminalis, isoproterenol 400 68 0.239 (isoproterenol vs. no isoproterenol) Crista terminalis, no isoproterenol 425 85 0.239 (isoproterenol vs. no isoproterenol) major procedural complications. Crista terminalis, superior origin 407 91 0.420 (ANOVA comparison by anatomic site) An electroanatomic mapping system (CARTO or Crista terminalis, mid origin 418 67 0.420 (ANOVA comparison by anatomic site) NavX) was used for the initial procedure in 72 cases Crista terminalis, inferior origin 379 86 0.420 (ANOVA comparison by anatomic site) (Figures 1, 2, and 4). Mapping was focused on the region of interest, and a mean of 89 37 points were fi Multiple analyses of variance (ANOVA) versus all AT groups. *Statistically signi cant. fl Abbreviations as in Tables 2 and 3. taken.Comparedwiththeuseof uoroscopy alone for catheter guidance, the use of a mapping system

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FIGURE 4 Activation Maps of Crista Terminalis Atrial Tachycardia FPO = print & web 4C

(A) Activation map for an example of focal atrial tachycardia arising from the superior crista terminalis. Modiﬁed posteroanterior view is shown with the crista terminalis viewed en face, conduction in the inferior (*) and medial († [across the intercaval region toward the inter-atrial septum]) directions. (B) Activation map for an example of focal atrial tachycardia arising from the inferior crista terminalis. (Bi) Modiﬁed posteroanterior (PA) view with caudal tilt showing the inferior crista terminalis en face. There was conduction block in the medial direction (x), and conduction was fastest in the inferior direction (*) with breakout across the cavotricuspid isthmus. (C) Conduction velocity (mean SD) in each direction from the site of origin for crista terminalis atrial tachycardia; conduction in the superior/inferior axis was faster than the lateral axis (***p < 0.0001). Abbreviations as in Figures 1 and 2.

increased the chance of single-procedure acute suc- and inferior directions along the long-axis of the cess for crista terminalis AT from 86.6% to 98.5% (p < crista terminalis (Figures 2 and 4). The mean con- 0.05) and reduced the ﬂuoroscopy time from 20.4 duction velocities were as follows: superior, 0.82 1.3 min to 16.4 1.2 min (p < 0.05). 0.19 m/s; inferior, 0.90 0.20 m/s; medial, 0.30 Electroanatomic activation maps were used to 0.17 m/s; and lateral, 0.39 0.24 m/s (Figure 4). calculate the conduction velocity away from the Conduction velocities in the superior and inferior pointoforigininthesuperior, inferior, medial (to- directions were signiﬁcantly faster than in the lateral ward the septum), and lateral (toward the pectinate and medial directions (p < 0.001), consistent with right atrial muscle) directions. Using this approach, knownconductionanisotropyinthisregion(Online preferential conduction was observed in the superior Data, Online Table 3).

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TABLE 5 Second Arrhythmia Diagnosed at Index Electrophysiological Study

AVNRT p Value CTI-Dependent Flutter p Value Atrial Fibrillation p Value AVRT p Value All sites 9.7 (42) 0.0015* 5.1 (22) 0.077 (NS) 2.5 (11) 0.579 (NS) 0.91 (4) 0.866 (NS) Crista terminalis 17.07 (28) <0.0001* 9.8 (16) 0.005 (NS) 3.7 (6) 0.220 (NS) 1.8 (3) 0.141 (NS) Tricuspid annulus 0 (0) 0.005 (NS) 1.8 (1) 0.497 (NS) 1.8 (1) 0.999 (NS) 1.8 (1) 0.400 (NS) Coronary sinus 11.9 (5) 0.590 (NS) 4.8 (2) 0.999 (NS) 0 (0) 0.612 (NS) 0 (0) 0.999 (NS) Peri-nodal 15.4 (4) 0.271 (NS) 0 (0) 0.623 (NS) 0 (0) 0.999 (NS) 0 (0) 0.999 (NS) Mitral annulus 7.4 (2) 0.999 (NS) 0 (0) 0.627 (NS) 0 (0) 0.999 (NS) 0 (0) 0.999 (NS) Bachmann’s bundle 0 (0) 0.999 (NS) 0 (0) 0.999 (NS) 0 (0) 0.999 (NS) 0 (0) 0.999 (NS) Septal 3.1 (1) 0.343 (NS) 0 (0) 0.386 (NS) 0 (0) 0.999 (NS) 0 (0) 0.999 (NS) Pulmonary veins 3.5 (2) 0.143 (NS) 3.5 (2) 0.754 (NS) 7.0 (4) 0.036 (NS) 0 (0) 0.999 (NS) Right atrial appendage 0 (0) 0.241 (NS) 5 (1) 0.999 (NS) 0 (0) 0.999 (NS) 0 (0) 0.999 (NS) Left atrial appendage 0 (0) 0.999 (NS) 0 (0) 0.999 (NS) 0 (0) 0.999 (NS) 0 (0) 0.999 (NS)

For p values, Fisher exact test, p < 0.05 significance for group analysis; p value for significance for pairwise comparisons by Bonferroni correction, p < 0.005. Values are n (%). *Statistically significant. AVNRT ¼ atrioventricular nodal re-entry tachycardia; AVRT ¼ atrioventricular re-entry tachycardia; CTI ¼ cavotricuspid isthmus.

ASSOCIATION WITH AF AND OTHER ATRIAL long-term freedom from arrhythmia. The patient ARRHYTHMIAS. Among patients undergoing ablation requiring 3 ablations was treated early in this series for crista terminalis AT, there was a significant asso- with the initial procedure date within the first 3 years ciation with a second atrial arrhythmia (Table 5). At of this dataset. At long-term clinical follow-up, of the the index electrophysiology study for crista termi- 153 patients who received ablation with eventual nalis AT, atrioventricular nodal re-entry tachycardia procedural success, 149 reported complete resolution (AVNRT) was also diagnosed in 28 patients (17.1%), of their symptoms and no recurrence over the mean and this finding was significantly more common than follow-up period of 91 months (maximum, 198 for AT arising from all other sites (9.7%; p < 0.0001). months; minimum, 7 months). Another 4 patients For these patients with AVNRT, the primary reported infrequent palpitations but underwent arrhythmia was diagnosed as crista terminalis AT by repeated Holter monitoring and had no documented the treating physician based on comparison of pro- recurrence of their clinical tachycardia. Two patients cedural data versus the clinical tachycardia (12-lead had died of unrelated noncardiac conditions. ECGs and Holter monitor). The precise anatomic Two patients with successful ablation and no localization of the crista terminalis AT in these 28 recurrence of crista terminalis AT were diagnosed patients was inferior crista terminalis in 4, mid crista with AF 5 and 7 years after the index procedure and terminalis in 14, and superior crista terminalis in 10 commenced treatment with sotalol and flecainide, (p ¼ 0.33). respectively. No other patients reported a diagnosis There was no significant difference in the fre- of AF at late follow-up, but systematic monitoring quency of atrioventricular re-entry tachycardia be- was not performed. Three other patients remained on tween the anatomic sites (Table 5). Six patients with metoprolol for palpitations unrelated to AT, having crista terminalis AT (3.7%) had at least 1 episode of no SVT documented on Holter monitoring (Table 1). paroxysmal AF documented before the procedure; this finding was not significantly different from AT DISCUSSION from all other sites.

LONG-TERM FOLLOW-UP OF CRISTA TERMINALIS To the best of our knowledge, electrophysiological AT. Telephone follow-up was completed for all pa- characteristics and acute and long-term outcomes for tients with previous successful ablation for crista tachycardias originating from the crista terminalis terminalis AT. Of the 154 patients with a successful have not been described in a large series with long- ablation, there were 15 documented recurrences in term follow-up. Our study showed that compared the ﬁrst year (9.7%). These patients underwent an with patients with other AT sites of origin, crista additional procedure; in 1 patient, repeat ablation was terminalis AT patients were older, more commonly not attempted because of phrenic nerve capture at female, were more commonly associated with coex- the ablation target (the earliest site of activation). All istent AVNRT, and were more likely to be inducible other patients achieved eventual long-term success, with programmed stimulation. The acute ablation although 1 patient required a third ablation to achieve success rate was high and improved signiﬁcantly

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when 3D mapping was used. Recurrence in the first 12 CENTRAL ILLUSTRATION Clinical Features and Ablation months after a successful ablation was uncommon. In Outcomes of Focal Atrial Tachcyardia Arising From the Crista > long-term follow-up of 7years,althoughsystematic Terminalis monitoring was not performed, only 2 patients had received a clinical diagnosis of AF (Central Illustration). Characteristics Female predominance (72.9%) FPO Older age at presentation (57 yr) = MECHANISM OF CRISTA TERMINALIS AT. In the se- Programmed stimulation for initiation (81.5%) ries presented here, the crista terminalis was the most Superior-Inferior preferential conduction common site of AT, accounting for 31% of all AT, Co-existing AVNRT (17.1%) similar to previous studies (2). The reason for this finding may be the unique electrophysiological print & web 4C properties of the crista terminalis; the normal crista terminalis is functionally distinct from the sur- rounding 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). Focal Atrial Tachycardia Although the crista terminalis has these distinct Crista Terminalis (n = 171) vs all other sites (377) 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 Ablation Outcomes sites, providing insight into the mechanisms and High success (92.2% single procedure) pathology. A high proportion of crista terminalis AT No major complications required PES for initiation (81.5%), indicating micro Low incidence of atrial fibrillation on long term re-entry as the probable dominant arrhythmia follow up (1.1%) mechanism. In addition, the mean age of patients with crista terminalis AT was w10 years older than Morris, G.M. et al. J Am Coll Cardiol EP. 2019;-(-):-–-. patients with AT from other sites (57.0 13.5 vs. 47.3 18.4 years, respectively), suggesting that The central panel shows local activation time for a focal atrial tachycardia that was crista terminalis remodeling is important in the successfully ablated at the superior crista terminalis, note the preferential conduction in generation of the arrhythmia substrate. With the supero-inferior direction. The upper panel lists the principle clinical characteristics of atrial tachycardias arising at the crista terminalis, the lower panel summarizes ablation advancing age, preferential remodeling at the crista outcomes. LAT ¼ local activation time. terminalis has been previously reported with an in- crease in anatomically determined functional conduction delay at this site (10). In further support of difference is driven by the sex difference of crista the role of re-entry as the main arrhythmia mecha- terminalis AT. The reasons for the observed female nism, our data show significant conduction anisot- propensity are not clear; among patients without ropy at the crista terminalis, with preferential crista terminalis AT, there is no evidence for sex conduction in the superior-inferior axis and slowed differences in atrial electrophysiology at any site conduction in the lateral-medial axis. There was a within the right atrium (11). significant excess of female patients with crista terminalis AT (72.9%) that was not seen in AT from RELATIONSHIP WITH AF AND OTHER ARRHYTH- other sites (50.8%). AT as a mechanism of SVT has MIAS. Although crista terminalis foci have been previously been reported to be more common in implicated in the initiation of AF (12–14),inourseries female patients (1), and our data suggest that this of 171 patients who presented with a clinical rhythm

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of focal AT, only 2 developed AF in 7 years of follow- further suggesting the presence of conduction up, suggesting that crista terminalis AT does not seem slowing. to be a risk factor for late development of AF. Patients STUDY LIMITATIONS. Data collection was retrospec- with a previous ablation for AF were excluded from tive. Detection of atrial fibrillation was based on the analysis. This implies that the age-related symptoms, therefore asymptomatic AF may have remodeling that leads to the development of crista been missed. Long-term follow up of AT from other terminalis AT is likely a local rather than a diffuse sites was not undertaken for comparison. process in these patients. Although systematic monitoring for asymptomatic AF was not performed, CONCLUSIONS we believe that the low rate of symptomatic AF is striking and generally indicates a low likelihood that The crista terminalis is the most common site of crista terminalis AT is the forerunner of AF. origin for AT; this arrhythmia is more common in Theprevalenceofasecond atrial arrhythmia women, is more likely to require PES for initiation, treated or diagnosed at the index procedure for crista and presents later in life than other AT, suggesting a terminalis AT was 31%, and it may be that the AT is role for re-entry and age-related remodeling in its acting as an initiating trigger for the second atrial pathogenesis. However, the remodeling seems to be arrhythmia for which there is a coincident underlying localized because progression to AF after successful substrate. However, there was a significant associa- treatment was rare. Coexisting AVNRT was common tion with AVNRT (17.1%) not seen with AT from other in this group, and radiofrequency ablation had a high sites. This finding raises the possibility in these cases success rate with low complications and good long- that remodeling of the crista terminalis has both term freedom from atrial arrhythmia. caused crista terminalis AT and modified the substrate for AVNRT. The reason for this outcome is not ADDRESS FOR CORRESPONDENCE: Dr. Jonathan M. clear; however, it may be hypothesized that remod- Kalman, Department of Cardiology, The Royal Mel- eling of the inferior portion of the crista terminalis bourne Hospital, Grattan Street, Parkville, Victoria– might affect a portion of the slow pathway or alter 3050, Australia. E-mail: [email protected]. the electrical coupling of the atrium to the slow pathway, thus increasing the probability of AVNRT PERSPECTIVES induction. Anatomically, the crista terminalis ex- tends into the Eustachian ridge, across the orifice of COMPETENCY IN MEDICAL KNOWLEDGE: The the inferior vena cava toward the coronary sinus crista terminalis is the most common site for focal AT ostium near the proximal segment of the slow and thus will be frequently encountered by cardiolo- pathway (6). In this region, there is evidence of gists and electrophysiologists. These results show “nodal” type tissue (i.e., similar to the crista termi- that it is a disease of age-related localized remodeling nalis) (15–17), and thus a theoretical possibility exists at the crista terminalis, and therefore treatment by that remodeling of the crista terminalis could extend ablation should be considered because it has excellent to this region near the slow pathway; this theory is long-term success rates, low complication rates, and unproven, however. little evidence of progression to other atrial arrhythmias. Intriguingly, there was an association with ABLATION OUTCOMES. Overall acute ablation suc- AVNRT; thus, crista terminalis AT should be consid- cess was high (92.2%); with the use of 3D mapping ered as a differential diagnosis when patients present later in the series, it improved further to 98.5%. The with palpitations after an ablation for AVNRT. crista terminalis is a muscle bundle up to 10 mm thick (6), which is at the limit of lesion depth formation by TRANSLATIONAL OUTLOOK: Although the crista radiofrequency ablation (18).Furthermore,thecrista terminalis is understood to be an area with unique terminalis is frequently penetrated by the sinus node electrophysiological properties (e.g., compared with arterial (6),which,ifpresent,wouldhaveacooling atrial muscle, it expresses low conductance gap effect, reducing the effectiveness of ablation. Under junction proteins and higher levels of HCN channels these conditions, the high acute success rate for conferring automaticity), the additional remodeling ablation of crista terminalis AT suggests an endocar- required to cause clinical AT is unknown. Further dial critical zone of superficial conduction slowing, detailed investigation of the changes occurring with rendering the tachycardia very sensitive to ablation. aging in this region may help to reveal the mechanism. The bipolar electrogram at the site of successful ablation was predominantly fractionated (63%),

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FLA 5.5.0 DTD JACEP863_proof 13 March 2019 7:08 am ce Atrial Tachycardia Arising From the Crista Terminalis, Detailed Electrophysiological Features and Long-Term Ablation Outcomes Gwilym M. Morris, Louise Segan, Geoff Wong, Gareth Wynn, Troy Watts, Patrick Heck, Tomos E. Walters, Ashley Nisbet, Paul Sparks, Joseph B. Morton, Peter M. Kistler, Jonathan M. Kalman The crista terminalis is known to be the most common site for focal atrial tachycardia (AT). This 0000 study identified 171 ablation procedures for crista terminalis AT. Compared with patients with other AT, crista terminalis patients were older (57.3 years), more commonly female (72.9%), and were more likely to require programmed stimulation (81.5%). The endocardial ablation success rate was 92.2%, and the first-year recurrence was 9.7%. In long-term follow-up, 2 patients developed atrial fibrillation. These features suggest that age-related remodeling causes a superficial endocardial zone of conduction slowing leading to re-entry. Ablation outcomes were good, with long-term freedom from atrial arrhythmia.

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