Safety and efficacy of catheter ablation of atrial fibrillation in the very elderly (≥80 years old): Insights from the UC San Diego AF Ablation Registry

Abstract Background Catheter ablation improves outcomes in symptomatic atrial fibrillation (AF) patients. However, its safety and efficacy in the very elderly (≥80 years old) is not well described. Hypothesis Ablation of AF in the very elderly is safe and effective. Methods We performed a retrospective study of all patients who underwent catheter ablation enrolled in the University of California, San Diego AF Ablation Registry. The primary outcome was freedom from atrial arrhythmias on or off antiarrhythmic drugs (AADs). Results Of 847 patients, 42 (5.0%) were 80 years of age or greater with a median age of 81.5 (80–82.3) and 805 (95.0%) were less than 80 years of age with a median age of 64.4 (57.6–70.2). Among those who were ≥80 years old, 29 were undergoing de novo ablation (69.0%), whereas in the younger cohort, 518 (64.5%) were undergoing de novo ablation (p = .548). There were no statistically significant differences in fluoroscopy (p = .406) or total procedure times (p = .076), AAD use (p = .611), or procedural complications (p = .500) between groups. After multivariable adjustment, there were no statistically significant differences in recurrence of any atrial arrhythmias on or off AAD (adjusted hazard ratio [AHR]: 0.75; 95% confidence interval [CI]: 0.45–1.23; p = .252), all‐cause hospitalizations (AHR: 0.86; 95% CI: 0.46–1.60; p = .626), or all‐cause mortality (AHR: 4.48; 95% CI: 0.59–34.07; p = .147) between the very elderly and the younger cohort. Conclusion In this registry analysis, catheter ablation of AF appears similarly effective and safe in patients 80 years or older when compared to a younger cohort.

Atrial fibrillation (AF) has become increasingly prevalent and its incidence increases with aging, with over half of AF patients projected to be over the age of 80 by 2050. 1,2Catheter ablation has emerged as a viable alternative to long-term pharmacologic antiarrhythmic therapy for rhythm control of AF and will likely be used more commonly given its inclusion in guidelines and increasing evidence in favor of an early rhythm control strategy. 3,4However, the management of AF in the elderly is complicated by concurrent comorbidities, age-related physiological changes, and frailty. 5,69][10] The safety and efficacy of catheter ablation in the very elderly (≥80 years old) population is thus not as well described. 11atients were stratified into groups based on whether they were 80 years of age and older or younger than 80 years of age.Clinical outcomes were determined during all follow-ups and included inhospital adverse events, recurrence of atrial arrhythmia at final follow-up on or off antiarrhythmic drugs (AAD) and off AAD, allcause hospitalizations, and mortality.Arrhythmia recurrence was defined as AF, atrial flutter (AFL), or atrial tachycardia (AT) lasting ≥30 seconds recorded on a 12-lead electrocardiogram (ECG), on ambulatory monitoring, or on implantable device interrogation, as recommended by contemporary guidelines. 12Patients who were continued on AAD after the 3-month blanking period were censored from the analysis assessing recurrence of atrial arrhythmias off AAD.
Adverse events were recorded in the registry and included access site complications (e.g., bleeding, groin hematoma, pseudoaneurysm, and arteriovenous fistula), cardiac perforation or tamponade, stroke or transient ischemic attack, pericarditis, myocardial infarction, atrioesophageal fistula, phrenic nerve injury, and pulmonary vein stenosis.
As part of the registry, follow-up arrhythmia monitoring was prespecified and was recommended as a 12-lead ECG at each followup visit, along with routine ambulatory ECG monitoring (24-hour Holter monitor, extended ambulatory ECG monitoring, or event monitoring) in all patients at 6 months, 1 year, and 2 years after ablation and additional ambulatory ECG monitoring to evaluate for arrhythmia recurrence in the presence of suggestive symptoms, which was consistent with consensus guidelines and updated consensus guidelines at the time of the registry. 12,13formed consent was obtained before all ablation procedures.General anesthesia was used in all cases.Intravenous heparin was administered to target an activated clotting time of 300-400 seconds before and during left atrial access.A transseptal puncture was performed under direct visualization with intracardiac echocardiography.Pulmonary vein isolation was performed using segmental, circumferential, or both types of ablations at the discretion of the operator.Closed and open irrigated and noncontact and contact force sensing catheters were used at the discretion of the operator.
Electroanatomic mapping systems were used in all cases (CARTO TM , Biosense-Webster Inc. or Ensite TM , St. Jude Medical Inc.).Pulmonary vein entrance and exit block were confirmed with the use of a circular catheter, and adenosine and isoproterenol were administered at the operator's discretion.Additional lesion sets including a cavotricuspid isthmus line, left atrial roof line, posterior mitral isthmus line or anterior line, coronary sinus ablation, and ablation of complex fractional atrial electrograms were performed at the discretion of the operator.
Continuous variables are presented by group as means ± 1 standard deviation for normally distributed variables and as medians with 25th and 75th percentiles for variables that were not normally distributed.Comparison between all groups was done using the nonparametric Kruskal-Wallis tests.All possible comparisons among groups were performed using the Student t-test if the data were normally distributed or the Wilcoxon rank-sum test if the data were not normally distributed.Categorical variables were reported as count and percentage, with the χ 2 or Fisher exact test (expected cell counts < 5) used for comparisons.
Recurrence of atrial arrhythmias at the final follow-up was analyzed using the Kaplan-Meier method with a 3-month blanking period and log-rank significance testing.Unadjusted and adjusted Cox proportional hazards modeling was used to analyze recurrence of atrial arrhythmias with a 3-month blanking period and results are presented as hazard ratios (HRs) with 95% confidence intervals (CIs).Patients who were lost to follow-up were censored at the date of last known follow-up.Covariates included in the adjusted model are presented in Table 1, which were selected based on a clinically plausible association of the predictor variable with recurrence of the primary outcome of recurrent atrial arrhythmias.Missing values were minimal and roughly equivalent between groups for all variables and were thus omitted.Analyses were performed using Stata 11 (StataCorp LLC) statistical software.A p < .05 was considered statistically significant.
T A B L E 1 Baseline characteristics.There were no statistically significant differences in prevalence of procedural complications between groups (Table 2).Recurrence of atrial arrhythmias on or off AAD (50.0% vs. 46.1%;log-rank p = .897)and off AAD (47.6% vs. 45.6%;log-rank p = .762)was statistically similar in the very elderly compared to the younger control group during follow-up (Figure 1A,B).Patients were on AAD after the 3-month blanking period in 17 (40.5%) of the very elderly and in 360 (44.7%) patients in the younger control group (p = .126).There was no statistically significant difference in the frequency of patients undergoing repeat ablation in the very elderly group compared to the younger control group (26.2% vs. 24.8%;p = .819).
Unadjusted rates of all-cause hospitalizations (42.9% vs. 26.6%;log-rank p = .022)and all-cause mortality (14.2% vs. 1.6%; log-rank p < .001)were higher in the very elderly group compared to the younger control group during follow-up (Figure 2A,B).However, this was no longer the case after multivariable adjustment.HRs with multivariable adjustment for potential confounders and respective CIs for recurrence of atrial arrhythmias and all-cause hospitalizations and mortality are summarized in Table 3.

| DISCUSSION
In this retrospective cohort study, catheter ablation of AF appears to be similarly effective and safe in patients 80 years of age or older when compared to a younger cohort.The very elderly (≥80 years old) was selected as the study group as they were previously underrepresented in studies of catheter ablation of AF.][9][10] Although another previous study evaluated the safety of catheter ablation in this population, with data reported on both procedural complications and mortality, 11 it did not report data on the efficacy of catheter ablation in  Note: Values are presented as median (Q1, Q3) for continuous variables or n (%) for categorical variables.
b Other complications included myocardial infarction, atrioesophageal fistula, phrenic nerve paralysis, and pulmonary vein stenosis.
| 1491 preventing recurrence of AF in this patient population.In this study, recurrence rates of atrial arrhythmias both off and on or off AADs were similar between groups over 5 years of follow-up.Similar to what was previously published, rates of all-cause hospitalizations and mortality in this study were also not significantly different between groups after multivariable adjustment.
The presence of more comorbidities in the very elderly group, such as coronary artery disease and hypertension, argues against selection bias.However, frailty is not taken into account as it is difficult to objectively quantify and it could thus be argued that the least frail, very elderly patients were chosen for a catheter ablation strategy.
The current analysis adds more to pre-existing literature as it evaluated in-hospital and long-term outcomes on both the safety and efficacy of catheter ablation in the very elderly (≥80 years old)  population compared to a younger cohort.Despite the age difference, there was no statistically significant difference in followup between groups, with a median follow-up of over 3.5 years in the very elderly group.Rhythm control with an ablation strategy is thus feasible in select elderly patients and there should not be an age limit above which patients are not considered for ablation.However, the median age of the very elderly group was 81.5, so it remains unanswered how safe and effective ablation of AF is in an even older population.These findings are significant as AF is the most common arrhythmia in the elderly, with the prevalence expected to increase over the next several decades. 14Although large studies have previously been published on the safety and efficacy of AF in elderly cohorts, the long-term follow-up involving outcomes such as atrial arrhythmia recurrence, hospitalizations, and mortality compared to a younger cohort makes these findings valuable. 15,16ven a subset of patients remain symptomatic despite rate control, a rhythm control strategy is often pursued, especially since the higher rates of comorbidities present in the elderly population can make the use of AADs challenging.Furthermore, catheter ablation has been shown to be more effective in maintaining sinus rhythm and improving functional status and quality of life in the elderly compared to AADs. 10 Despite these advantages, catheter ablation of AF is often not considered as a viable alternative in the elderly due to concerns for safety and efficacy, which is largely due to the lack of data in this population.
Although catheter ablation does carry an increased risk of embolization, uninterrupted anticoagulation has been shown to reduce thromboembolic events to less than 1% without increasing bleeding complications. 17However, there is currently little data on the safety and efficacy of uninterrupted anticoagulation during catheter ablation of AF in elderly patients.Still, this study and previously published studies have shown that anticoagulants, both vitamin K antagonists and direct oral anticoagulants, can be prescribed in the periprocedural period without significantly increasing bleeding risk. 18

| Study limitations
There are some limitations to interpreting the data presented in this study.First, the generalizability may be limited given that this study involved a single center and was a retrospective analysis.
Second, the very elderly (≥80 years old) group was small in number relative to the control group.Third, it could be argued that very elderly (≥80 years old) patients selected to undergo catheter ablation were relatively healthier than the average patient in that age group; however, multivariable modeling was performed to account for differences in groups.Fourth, there was no standardized duration of monitoring for AF recurrence as it was left to the discretion of the clinician.However, at the minimum, guidelinebased recommendations were followed in all cases. 12Fifth, a significant percentage of patients were lost to follow-up after 2-3 years.

| CONCLUSION
Catheter ablation of AF appears to be similarly effective and safe in patients 80 years of age or older when compared to a younger cohort.There were no significant differences in all-cause hospitalizations, mortality, or rates of recurrence of atrial arrhythmias.

F I G U R E 1
Kaplan-Meier plots of (A) long-term recurrence of atrial arrhythmias (AF/AFL/AT) on or off antiarrhythmic drugs (excluding a 3-month postprocedural blanking period), and (B) longterm recurrence of atrial arrhythmias (AF/AFL/AT) off antiarrhythmic drugs.Patients who were 80 years of age or older and a younger cohort are compared.AAD, antiarrhythmic drug; AF, atrial fibrillation; AFL, atrial flutter; AT, atrial tachycardia.F I G U R E 2 Kaplan-Meier plots of (A) long-term rate of all-cause hospitalizations and (B) long-term rate of all-cause mortality.Patients who were 80 years of age or older and a younger cohort are compared.T A B L E 3 Adjusted HRs and CIs.
T A B L E 2 Comparison of ablation characteristics and complications.