Safety and efficacy of ablation index‐guided atrial fibrillation ablation in octogenarians

Abstract Background Limited data on the efficacy and safety of atrial fibrillation (AF) ablation using an ablation index (AI) for octogenarians is available. We aimed to compare the efficacy and safety of AI‐guided AF ablation between AF patients aged ≥80 years (Group 1) and <80 (Group 2). Hypothesis We hypothesized that AI‐guided AF ablation could complete the procedure with comparable efficiency and safety in patients aged ≥80 years and <80. Methods We retrospectively reviewed 2087 AF patients undergoing their first AI‐guided AF ablation in our hospital. We compared the atrial tachyarrhythmia (AT) recurrence and procedure‐related complication rate between Group 1 (n = 193) and Group 2 (n = 1894). Results The mean age was 83.0 (interquartile range [IQR] 81.0, 84.0) years in Group 1 and 67.0 (IQR 60.0, 72.0) in Group 2. AF type was significantly different between the two groups: Of Group 1 patients, 120 (62.2%) had paroxysmal AF, 61 (31.6%) persistent AF, and 12 (6.2%) long‐standing persistent AF, while of Group 2 patients, 1016 (53.6%) paroxysmal AF, 582 (30.7%) persistent AF, and 296 (15.6%) long‐standing persistent AF (p = .001). Unadjusted AT recurrence‐free survival curves showed similar AT recurrence‐free survival between the two groups (p = .67 by log‐rank test). After the adjustment for AF type, the survival curve was similar between them (hazard ratio, 1.24; 95% CI [0.92–1.65]; p = .15, Group 1 vs. Group 2). The rate of procedure‐related complications was similar between the two groups (3.1% vs. 3.0%, respectively, p = .83). Conclusion Catheter ablation guided by AI achieved similar AT recurrence and complication rates between elderly AF patients aged ≥80 years and patients <80 years.

The incidence of atrial fibrillation (AF) increasingly grows due to the growing number of the aged population. 1,2 Elderly patients often have comorbidities, including hypertension, diabetes, chronic renal disease, coronary artery disease, or stroke. 3 These comorbidities complicate the medical management of AF, and especially, treatment with antiarrhythmic drugs is often difficult due to the increased risk of adverse effects in the elderly.
Catheter ablation has been established as the rhythm control strategy for AF, and pulmonary vein (PV) isolation (PVI) is the cornerstone of catheter ablation for AF. 4 With the advancement of ablation technology enabling the operators to complete PVI efficiently, the outcome and safety of the AF ablation procedure have been improved. In radiofrequency (RF) catheter ablation, the ablation index (AI) is a quantitative ablation lesion size marker that considers contact force, RF application time, and RF power in a weighted formula, and AI guidance was reported to minimize recurrence after AF ablation. [5][6][7] Also, AI-guided, high-power RF application was the technical method to shorten the procedure time. 8 Recently, AI-guided high-power RF catheter ablation for elderly AF patients older than 75 was reported to be safe and effective. 9 However, limited data on the efficacy and safety of AIguided ablation procedures for very elderly AF patients have been available.
We previously reported the effects of AI-guided AF ablation in a large number of AF patients. 10 In this present study, we compared the atrial tachyarrhythmia (AT) recurrence and complications between AF patients aged ≥80 years and <80 years to elucidate the effects of AI-guided AF ablation in very elderly AF patients.

| Study population
We included 2087 patients undergoing the first AI-guided RF catheter ablation for AF from January 2018 to June 2022. Our institution's ethics committee approved our study (approval number 776), and we obtained written informed consent from all patients before the procedure.
Before the procedure, we performed transesophageal echocardiography in patients with CHADS2 score ≥2, persistent AF, or a history of cerebral infarction or systemic thromboembolism to rule out the left atrial (LA) thrombus. All patients were administered an anticoagulant for >4 weeks before the procedure. Warfarin was not interrupted before and after the procedure. In patients taking direct oral anticoagulants, the drugs were continued before the procedure, were held in the morning of the ablation day, and were resumed 4 hours after the procedure unless major bleeding events occurred.
The patients taking rivaroxaban or edoxaban in the evening continued this evening dose during the periprocedural period. The anticoagulants were continued for at least 3 months after ablation.

| Cardiac catheterization
The procedure was performed while the patients were in the fasting state. Majority of the patients (94.4%) underwent the procedure under local anesthesia and conscious sedation with dexmedetomidine and thiamylal, and respiratory management devices such as a nasal airway device and adaptive servo-ventilation were used at the operator's discretion. The other 5.6% patients underwent the procedure under general anesthesia at the operator's discretion or the patient's preference. A 6Fr, double-decapolar, steerable catheter (BeeAT; Japan Lifeline Co.) was inserted into the coronary sinus via the right internal jugular vein. We inserted an 8Fr SoundStar ultrasound catheter (Biosense Webster) into the right atrium via the right femoral vein. We performed anatomical mapping of the LA by CartoSound module equipped with a CARTO3 system. After the transseptal puncture was done under intracardiac echocardiography, we inserted two 8. In all patients, the position of the esophagus was confirmed by the contrast medium swallowed by the patients just before catheterization or intracardiac echography from the LA as reported previously. 11

| AF ablation procedure
We performed circumferential PVI by creating linear RF application on the ipsilateral PV antrum and intervenous carina in the integrated three-dimensional image in all patients, as reported previously. 10 We used an 8-Fr irrigation catheter (ThermoCool SmartTouch Surround Flow; Biosense Webster) for point-to-point RF ablation. We set the AI target value at ≥400 at the anterior LA wall, ≥360 at the posterior LA wall, and ≥260 at the LA wall on the esophagus. We set RF power at 30-40 W in the anterior LA wall, 20-25 W in the posterior LA wall, and 20 W LA wall on the esophagus until October 2018, and we adopted a high-power RF application set as follows: 50 W in the anterior LA wall, 40 W posterior LA wall, and 25 W on the esophagus since then. In patients undergoing RF application with a high-power setting, 5 seconds 50 W RF applications with a contact force of <10 g was performed at the operators' discretion. We performed a 40-50 W RF application for the extra-PV site except for superior vena cava (SVC) isolation with the AI target value ≥ 360. In SVC isolation, we set the RF application power at 20-25 W and the AI target value ≥ 260 in all patients. We attempted to keep the contact force between 10 and 20 g during the RF application. We did not monitor esophageal temperature during the procedure but reduced the AI value on the esophagus visualized and delineated on the CARTO three-dimensional map. 11 We reapplicated RF to the area where AI value did not achieve the AI value target.
We performed electro-cardioversion when AF persisted after the circular RF application for circumferential PVI. Then we created LA and PV electroanatomical map during the right atrial (RA) pacing to confirm the disappearance of the PV and PV antrum potentials. We attempted to ablate any residual conduction gaps to complete circumferential PVI. The PV-to-LA conduction block was confirmed by pacing at 10-mA output from 10 pairs of the PentaRay Nav catheter placed at the ostium of the PV.
After completing circumferential PVI, we administered a bolus of 10-20 µg of isoproterenol intravenously to induce non-PV triggers, and if present, we attempted to ablate them. We defined the low voltage zone as the area of LA voltage <0.5 cm 2 over the size of 5 cm 2 . Extra-PV ablation procedures, including ablation of low voltage zone, ablation of LA roof linear ablation, posterior LA wall box isolation, anterior LA wall linear ablation, mitral isthmus linear ablation, and ablation for complex fractionated atrial electrogram, were performed at the operator's discretion. We performed the SVC isolation for all patients with SVC sleeve length >20 mm and CTI ablation for all patients with CTI-dependent atrial flutter.

| Follow-up
All patients were followed up at the outpatient clinic in our institution. At 1, 3, 6, 9, and 12 months after ablation, all patients were asked about the symptoms and underwent both 12-lead electrocardiogram (ECG) and 24-hour Holter ECG monitoring. A mobile ECG recorder was used at the discretion of the physician. AT recurrence was defined as any ATs lasting >30 seconds after a 3-month blanking period.

| Statistical analysis
Continuous variables with normal distribution were expressed as mean ± standard deviation (SD) and compared by Student's t test.
Continuous variables with nonnormal distribution were expressed as the median and interquartile range (IQRs) and compared by the Wilcoxon test. Categorical variables were expressed as numbers and percentages and compared by Fisher's exact or χ 2 test. We considered the patients who died 90 days after the procedure without AT recurrence as censored patients.
In the AT recurrence-free survival analysis, we analyzed the patients with >90 days of follow-up. We performed the unadjusted survival curve (Kaplan-Meier) and the adjusted Cox mortality curve analysis to compare the AT recurrence between the two groups. In the Kaplan-Meier analysis, we compared them by log-rank test. In the adjusted Cox mortality curve analysis, we compared the two groups while adjusting AF type because AF type strongly impacts the AT recurrence after AF ablation. We calculate the hazard ratio (HR) and 95% confidence interval (CI).
All tests were two-tailed, and p < . 05  paroxysmal AF and less long-standing persistent AF in Group 1 than in Group 2 (p = .001). More female patients in Group 1, and the prevalence of hypertension and sick sinus syndrome were higher in Group 1. Both serum creatinine and plasma brain natriuretic peptide levels were higher in Group 1, and both CHADS 2 and CHA 2 SDS 2 -VASc scores were higher in Group 1.

| AT recurrence
In the AT recurrence-free survival analysis, we excluded 64 patients without ≥90 days of follow-up and analyzed the remaining 2023 patients. Follow-up periods were slightly but significantly longer in Group  Figure 1A). One year AT recurrence-free T A B L E 2 Procedure characteristics. survival rate was 82.9% in Group 1 and 82.7 in Group 2. Figure 1B shows the survival curve adjusted for AF type, and Table 3 9 Our present study compared the AT recurrence-free survival rate and complications of AI-guided AF ablation between the patient groups aged ≥80 years and <80 years and showed similar AT recurrence-free survival rate and complication rate between the two groups even after adjustment of AF type. To the best of our knowledge, this is the first report evaluating the efficacy and safety of AI-guided AF ablation for patients aged ≥80 years compared with those for patients <80.

| Efficacy for elderly patients
In our present study, several patient and procedure characteristics were significantly different between the patient groups aged ≥80 years and <80. Especially, AF type was significantly different between the two groups, which might have significantly impacted the AT recurrence after the procedure. In the present patients aged ≥80 years, the percentage of paroxysmal AF was higher, and that of long-standing persistent AF lower than in those aged <80 years. Therefore, we compared the AF recurrence-free survival rate by the adjustment of AF type between the two groups and found a similar recurrence-free survival rate between the two groups. However, we did not adjust the other patient and procedural characteristics. In this study, the patients aged ≥80 were lean,  Note: Data are given as n (%).
had a higher percentage of hypertension and sick sinus syndrome, and had a higher plasma level of BNP. Further, the low voltage zone in the LA was more frequently observed in patients aged ≥80 years. These differences might have affected the outcome of AF ablation, but we did not adjust these parameters because all of these parameters deem to be strongly related to aging. Kanda et al. reported that cryoablation for elderly patients older than 80 years was similarly effective to those younger than 80. 19 This study also showed that several parameters, including hypertension, renal function, the value of NT-pro BNP, LAD, and low voltage zone, were significantly different between the patients older and younger than 80. They performed the Cox proportional hazard model analysis to adjust these parameters and showed that age ≥ 80 years was not an independent predictor for recurrence in cryoablation for AF. Our analysis revealed that even with the presence of multiple aging-related comorbidities, older age per se did not impact the AT recurrence after the AI-guided AF ablation.

| Limitation
This present study had some limitations. This study is a single-center retrospective study that included a small number of very elderly patients (n = 194). Frailty may impact the efficiency and safety of catheter ablation procedures, 21,22 but such frail patients were less likely to undergo ablation procedures and, therefore, underrepresented. The percentage of several extra-PV ablations was significantly different between the two groups. These differences might impact the outcome of the AF ablation procedure in these groups.
However, AT recurrence-free survival rates in the two groups were >80%, and the effects of the differences seem to be minimal. Followup periods were significantly different between the two groups.
However, the difference was small and seemed to have a limited impact on the analysis. We assessed the AT recurrence based on symptoms and periodically repeated ECG and Holter ECG recording, but not based on an implantable loop recorder. We might have underestimated the AT recurrence of asymptomatic paroxysmal AF.
We showed similar effectiveness of AI-guided AF ablation in patients aged ≥80 years to that in patients aged <80, but it is unknown whether such effectiveness is associated with improved quality of life and survival. The CABANA trial indicated that the ablation procedure reduced AT recurrence but did not reduce the clinically relevant event, including death, stroke, bleeding, and cardiac arrest, in elderly patients based on the intention-to-treatment analysis. 23 Catheter ablation for elderly AF patients without arrhythmia-related symptoms might have limited clinical benefits.

| Conclusion
AI-guided catheter ablation for elderly AF patients aged ≥80 achieved similar AT recurrence and complication rates to those younger than 80. A caution for cardiac tamponade should be required in elderly patients.

Ken Okumura received honoraria from Johnson and Johnson and
Medtronic. The remaining authors declare no conflict of interest.

DATA AVAILABILITY STATEMENT
The data supporting this study's findings are available on request from the corresponding author upon reasonable request. The data are not publicly available due to privacy or ethical restrictions.