Amr Kamal, M.D Alexandria Main University Hospital Alexandria- Egypt ECRA 2010

In order to consider AF ablation as a first line therapy, we should have clear and evidence based answers for the following 5 questions: 1) Do AF ablation really affects the short and long term outcomes in AF patients? 2) Do we have general consensus or agreement about the ideal AF ablation procedure ? ECRA 2010

3) Are AF ablation complications really happen uncommonly? 4) Are all AADs similar in safety and efficiency of rhythm control? 3) Is AF ablation procedure is cost effective ? ECRA 2010

I.Effects of RF Catheter Ablation of AF on Short- and Long-Term Outcomes ECRA 2010

There is only one fair-quality randomized, controlled trial that compared RFCA as first-line therapy with AADs in 67 patients reported a higher rate of freedom from recurrence of AF at 12 months with RFCA (87% vs. 37%) Wazni et al. JAMA 2005 ECRA 2010

No randomized, controlled trial examined the incidence of CHF in RFCA versus medical treatment of AF Only one poor quality observational study reported that patients who underwent RFCA had a lower risk for CHF than those receiving medical therapy (5% vs. 10%; P value not reported) at a mean follow-up of 30 months Pappone et al. JACC 2003 ECRA 2010

One fair-quality randomized, controlled trial of RFCA versus medical treatment reported no statistically significant differences in changes in left atrial diameter and left ventricular ejection fraction at 1-year follow-up Jaı¨s et al. the A4 study. Circulation ECRA 2010

Meta-analysis of six randomized, controlled trials found no statistically significant difference in the risk for cerebrovascular events at 12 months in patients who underwent RFCA compared with those who received medical therapy (risk difference, 0.6% [95% CI, - 1.1% to 2.3%]; medical treatment favored). Oral et al. NEJM 2006 Stabile et al. EHJ 2006 ECRA 2010

One poor-quality and 2 fair-quality RCT’s measured QOL by using the 36-item Short Form General Health Survey reported larger improvement in QOL score in patients who underwent RFCA BUT the net difference in score was only between 1 to 17 points, moreover, it is difficult to compare these results across studies because they were assessed at nonuniform time points. Krittayaphong et al. J Med Assoc Thai Oral et al. NEJM 2006 Jaı¨s et al. Circulation ECRA 2010

Two fair-quality RCT’s compared the rates or number of readmissions between RFCA and medical treatment groups. One trial reported a lower readmission rate in patients treated with RFCA than in those receiving medical treatment (9% vs. 54%) Wazni et al. JAMA 2005 ECRA 2010

Whereas the other reported no statistically significant difference in the median number of readmissions between RFCA and medical treatment (1 vs. 2 readmissions). Neither study provided the specific reasons for readmissions. Stabile et al. EHJ 2006 ECRA 2010

II.RFCA of AF Effects of Different Ablation Techniques ECRA 2010

o Overall success rates for PVI ranges between 47% to 83% at 12 m. o Nearly 20% to 40% of patients are taking AADs o Up to 30% of patients require a second procedure ECRA 2010

Five RCT’s compared the efficacy of one RFCA technique with or without the addition of left- sided ablation lines. Two studies of them did not find a significant difference in recurrence of AF with the addition of left sided ablation lines. Sheikh et al. J Interv Card Electrophysiol.2006 Pappone et al. Circulation ECRA 2010

One RCT examined the incremental benefit of adding a CTI ablation line in patients with AF and at least 1 episode of AFL who were undergoing RFCA for AF The investigators found no significant difference in recurrence of AF with the addition of CTI ablation at 12-month follow-up. Wazni et al. Circulation ECRA 2010

Another RCT compared WACA with versus without additional isolation of the SVC in patients with paroxysmal AF ; at 12-month follow-up, there was no significant difference in the recurrence of atrial tachyarrhythmia between the 2 groups. Wazni et al. JAMA 2005 ECRA 2010

III. RFCA of AF Complications and Harms ECRA 2010

52% success rate off AAD Additional 23.9% partial success rate of patients on AAD Median follow-up period of 11.6 months ECRA 2010

Meta-analysis of Eighty-four studies reported at least 1 adverse event associated with RFCA of AF Given that many studies had overlapping investigators, institutions, and years of enrollment, it is frequently difficult to ascertain whether patients had been included in multiple studies. Therefore, accurate estimates of adverse event rates across studies are not possible. ECRA 2010

IV. SAFETY AND EFFICIENCY OF NEW ANTIARRHYTHMIC DRUGS ECRA 2010

Choice of AADs for AF rhythm control: Antiarrhythmic therapy for AF is recommended on the basis of choosing safer, although possibly less efficacious, medication before resorting to more effective but less safe therapy. Dronedarone is a multichannel blocker that has a good safety profile especially in patients without structural heart disease and in stable patients with heart disease with a low potential for proarrhythmia ECRA 2010

V.COST EFFECTIVENESS OF AF ABLATION ECRA 2010

The cost of ongoing chronic medical therapy for AF equals that of AF ablation between 3.2 and 8.4 years of follow-up, with cost equivalence after 4 years on average. Most of studies have reported follow-up data that do not extend beyond 12 month, thus, the possibility of very late recurrences and associated health care expenditures remains open. Furthermore, late recurrence seems to be rather unpredictable. Khaykin et al. JCE 2007 ECRA 2010

One study presented data which evaluated the cost effectiveness of RFCA Vs. medical rate control therapy and medical rhythm control therapy with amiodarone. RFCA was not cost-effective in patients at low risk for stroke but could be cost-effective in moderate risk patients. Chan PS et al. JACC 2006 ECRA 2010

1. Evidence is insufficient to compare freedom from recurrence of atrial fibrillation in patients who had RFCA as first-line therapy with that in patients who received antiarrhythmic drugs. 2. Similarly, evidence is insufficient for comparing the rate of CHF between the RFCA and medical treatment groups. ECRA 2010

3. There is a low strength of evidence for finding no statistically significant difference between RFCA and medical therapy in the improvement of LA diameter or LV EF, or in the risk for cerebrovascular events at 12 months. 4. The strength of evidence is also low for suggesting that RFCA improves QOL, promotes avoidance of anticoagulation, or decreases readmission rates compared with medical treatment. ECRA 2010

5. Evidence is insufficient to make definitive conclusions about the effects of adding left- or right-sided ablation lines to RFCA. 6. The substantial heterogeneity of the additional ablation lines used in the different studies precludes meaningful comparisons. 7. Evidence is also insufficient to draw conclusions from retrospective studies. ECRA 2010

7. Most of the observational studies compared many different approaches to RFCA, and most studies used historical controls. 8. In some instances, the proportions of patients with different types of AF differed between groups, and follow-up results from different time points were compared between groups. ECRA 2010

9. Evidence is insufficient to draw conclusions in the studies that analyzed atrial fibrillation outcomes among different energy outputs, postprocedure durations of observation, various mapping techniques, or different ablation times because they all had deficiencies in study methods, moreover, none of the clinical studies adjusted for potential confounders. ECRA 2010

10. A low level of evidence showed that adverse events associated with radiofrequency catheter ablation are relatively uncommon. The level of evidence was rated low because of nonuniform definitions and assessments of adverse events across studies. ECRA 2010

Results from the Ablation Versus Anti-Arrhythmic Drug Therapy for AF (CABANA) trial should be available in late 2015 or This long-term trial of first-line therapies compares RFCA with either rate-control or rhythm-control AADs for reducing total mortality in patients with untreated or incompletely treated AF. Cost effectiveness and quality of life will be evaluated. ECRA 2010

1. Radiofrequency catheter ablation was superior to medical treatment at maintaining sinus rhythm at 1-year follow-up in patients with paroxysmal atrial fibrillation in whom medical therapy had failed. Thus, catheter ablation should be reserved for patients with AF which remains symptomatic despite optimal medical therapy, including rate and rhythm control. ECRA 2010

2. Most patients described in the studies were relatively young (mean age ~ 55 years) and had generally preserved LVEF (~ 0.60) and minimally increased LA diameter (~ 5 cm). Thus, results may not be generalizable to older patients with left ventricular dysfunction or severely dilated left atria. ECRA 2010

3. In addition, the primary end point in all published RCT’s to date has been the recurrence of AF, and no randomized trial has examined the effect of ablation on the risk for stroke or death. Thus, to fully assess such outcomes as stroke, death, or quality of life, much longer follow-up is needed. ECRA 2010

5. The published clinical studies are heterogeneous with regard to: o Monitoring for recurrence of AF (symptomatic vs. monitoring for asymptomatic episodes) o Reporting outcomes with or without repeated ablations o Separating rhythm control with from that without AADs after ablation. ECRA 2010

The differences in follow-up monitoring and management limit comparability across studies and reliable assessment of the effect of RFCA, thus, future studies should strive to adopt standardized postablation monitoring In addition, follow-up durations longer than the typical 6 to 12 months observed in the literature are needed before more reliable inferences can be made about longer-term efficacy of this procedure. ECRA 2010

To further understand why some patients benefit from radiofrequency ablation and some do not, future studies should implement a uniform system of defining the various types of atrial fibrillation and conditions under which outcomes were evaluated. ECRA 2010

For adverse event reporting, it was not always clear whether the lack of information on a particular adverse event meant that no events occurred or simply that the event was not assessed. In addition, the sample sizes in most studies were generally small, precluding reliable risk estimates of the adverse events. ECRA 2010

Many of the studies had a mean follow-up of no more than 12 months; any long term events (such as late recurrence or death) or delayed adverse effects from procedural radiation exposure could not be assessed. Furthermore, the lack of clarity regarding possible overlap in patients between studies severely hampered efforts to estimate event rates across all studies. ECRA 2010