Atrial fibrillation (AF) is the most common cardiac arrhythmia, becomes more prevalent with age,1 and is associated with an increased long-term risk for stroke, heart failure, and all-cause mortality.2 AF can occur in the absence of underlying heart disease, but is more frequent in connection with mitral valve disease, heart failure, ischemic heart disease, and hypertension.3
Over the past decade, catheter ablation has emerged as a promising approach for treating AF, and is now a commonly performed ablation procedure in major hospitals worldwide.4–10 Numerous studies from both randomized and non-randomized trials suggest that ablation is probably more effective than antiarrhythmic drugs in treating AF.5,8,9,11–13 However, most of these studies included a younger population of paroxysmal AF patients whose arrhythmias, in general, are not life-threatening or severely disabling.
The key question is then raised: what is the safety and efficacy of catheter ablation in the older and high-risk populations with AF, and could the benefits of maintaining sinus rhythm (SR) using the ablation approach yield the most sought-after outcomes of improved survival and reduced stroke rates in such patients? We described a new approach to AF ablation by identifying the target ‘substrate’ sites using electroanatomical mapping of complex fractionated atrial electrograms (CFAE).10 Our recent study also suggests that the catheter-based ablative approach may even have greater benefits for the elderly and high-risk populations with structural heart disease who suffer from AF.14 This article will discuss the results of this study with respect to mortality and stroke reduction after maintaining SR following successful catheter ablation.
High-risk Patients and Ablation of Atrial Fibrillation Substrates
Our study involved screening 2,356 high-risk AF patients similar to those in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial population.15 Patients were at least 65 years old or had at least one or more risk factors for stroke, including hypertension, diabetes, structural heart diseases (coronary artery disease, valvula cardiomyopathy, etc.), a prior history of stroke or transient ischemic attack (TIA), congestive heart failure (CHF), or a left ventricular ejection fraction (EF) of <40%. We excluded patients with chronic alcoholism, recent myocardial infarction within one month of the study, significant debilitating diseases or terminal disease, and those with documented left atrial thrombus. After the screening of these patients for catheter ablation (see Figure 1), we found 771 patients with symptomatic refractory AF who all had a high risk for stroke and, similar to those patients studied in the AFFIRM trial, were candidates for ablation.
All patients underwent non-fluoroscopic electroanatomical mapping with the CARTO™ mapping system (Biosense Webster, Inc., Diamond Bar). All electroanatomical maps were created for patients who were in AF, either spontaneously or by induction. CARTO provided a short cycle length (CFAE) map and enabled the operator to associate areas of CFAE with both atria and coronary sinus; the setting of the threshold was 0.05–0.15mV and the duration was 70–120 milliseconds.
We used bipolar maps and tags to recognize the CFAE points. We used bipolar recordings filtered at 30–500Hz and defined the CFAE as follows: fractionated electrograms composed of two or more deflections, and/or a perturbation of the baseline with continuous deflection of a prolonged activation complex; and atrial electrograms with a very short cycle length (<120 milliseconds). The CFAE was tagged and associated with the atrial anatomy created by CARTO, thereby identifying target sites for ablation.
RF applications were delivered via 8mm Navistar™ (Biosense-Webster, Diamond Bar California) with a maximal temperature of 55–60°C. The primary end-points during RF ablation were either complete elimination of areas with CFAE or conversion of AF to SR. When areas with CFAE were completely eliminated but the atrial arrhythmias persisted (organized atrial flutter or atrial tachycardia), they were subsequently mapped and ablated (occasionally in conjunction with ibutilide 1–2mg intravenously over 10–20 minutes). We used ibutilide to increase the cycle length of AF and to make it easier to find the target of ablation. If the arrhythmias were not successfully terminated, external cardioversion was performed.
Of the 771 patients, 674 underwent catheter ablations for AF; 39 were lost to follow-up within the three-month period after the ablation and were excluded from the study. Of the 97 patients who were not treated, 27 were excluded due to a left atrial thrombus and the other 70 patients declined the procedure. As shown in Figure 1, a total of 1,065 ablations were performed on our 635 patients. There were 329 patients (52%) who underwent one procedure, 204 patients (32%) who required two procedures, 80 patients (12.6%) who required the procedure three times, and only 22 patients (3%) who required four procedures.Maintaining Sinus Rhythm After Catheter Ablation
After a mean follow-up period of 836±605 days, 517 were in SR (81.4%). AF ablations are significantly more effective in maintaining SR in patients with paroxysmal AF (226 of 254 patients [90%]) and persistent AF (124 of 146 patients [86%]) compared with those with permanent AF (167 of 235 patients [70%]). Of the 517 patients who remained in SR, only 68 patients (13%) required antiarrhythmic agents to maintain SR (48 amiodarone, 19 sotalol, and 1 doefetilide).
Mortality Reduction After Maintaining Sinus Rhythm Following Ablation
Over the follow-up period there were 29 deaths: 15 patients who stayed in SR and 14 who remained in AF died. Patients whose AF ablation was effective in maintaining SR had a much lower five-year mortality rate (8%) than those with recurrent AF after the ablation (36%; p<0.0001) (see Figure 2).
It is possible that patients whose AF ablation failed to restore SR had more advanced heart disease or unrecognized risk factors that prevented them from maintaining SR and unfavorably influenced their overall survival. However, with the exception of the left atrial size and duration of AF, which were greater in patients who did not respond to AF ablation, there were no differences in terms of baseline patient characteristics, including EF. Multivariate analysis and Cox regression analysis convincingly show SR to be an independent predictor of a favorable prognosis, whereas EF, hypertension, and female gender had little effect. Sinus rhythm is an independent predictor of increased survival. Patients who maintained SR regardless of baseline EF had a lower mortality rate than their counterparts on the same corresponding EF stratum (see Figure 3).
The reason that patients who had a lower EF (<40%) but maintained SR fared better is probably the significant recovery of their ventricular function after restoring SR. The average EF increased from a mean of 31% prior to ablation to 41% following successful ablation (p<0.001). In contrast, patients who had recurrent AF after ablation had no change in their EF. Our data dovetail nicely with the findings of Hsu et al. that many AF patients with a depressed baseline EF show improvement in their EF after SR has been restored with a successful AF ablation.15
Stroke Reduction After Maintaining Sinus Rhythm
Warfarin therapy was discontinued in 434 patients (72.7%) whose AF was maintained after catheter ablation. Eleven patients experienced a major stroke or TIA. In the patients who discontinued warfarin, three patients developed a major stroke and two patients had a TIA compared with six patients in the group who required ongoing anticoagulation (five ischemic strokes and one fatal intracranial hemorrhage). The Kaplan-Meier curves for stroke rate are shown in Figure 4. The five-year stroke rate was 3% in the group of patients who were off warfarin compared with 23% in the group of patients who remained in AF and continued taking warfarin (p=0.004).
Procedure Complications
Five patients (0.9%) suffered from cerebrovascular accident (CVA). Incidentally, two of the five CVAs occurred 24–48 hours after the procedure. Hemopericardium occurred in seven patients (1.4%); one of these seven patients required cardiovascular surgical repair of the perforation of the left atrium at the ablation site, while the remaining six patients were treated successfully with pericardiocentesis. Nine patients developed major vascular complications at the groin sites (seven pseudoanerysm and two atrioventricular fistula). Two patients developed atrioventricular block and required permanent pacemaker implantation. Three patients had a transient pulmonary edema after the procedure.
Conclusion
Our study is the first to evaluate the safety and efficacy of catheter ablation in high-risk patients with AF. Our patients were much older than those in other studies with catheter ablation with AF. Despite these high-risk patients, our data clearly indicated that CFAE-targeted ablation of AF is effective in maintaining SR in selected high-risk AF patients and may allow patients to stop warfarin therapy. SR after AF ablation is a marker of relatively low mortality and stroke risk. Ablation is associated with mortality and/or stroke reduction. Our report here is from a single center; however, while needing further confirmation from large multicenter trials, these data are compelling and clearly suggest that catheter substrate ablation for controlling AF is a therapeutic modality whose time may have arrived.