CLEVELAND, OHIO. The Cleveland Clinic has finally released data concerning long-term success of pulmonary vein antrum isolation (PVAI) procedures with the aim of curing atrial fibrillation (AF). The study included 831 patients who underwent a PVAI in 2005. The average age of the patients was 59 years, 78% were male, and 86% had no underlying heart disease (lone AF). The majority (69%) had paroxysmal afib, 20% had the persistent variety, and the remaining 11% had permanent (long-standing persistent AF). All patients underwent PVAI, and 79% also had ablation at the superior vena cava. The study participants were followed for an average of 55 months, with the most recent update in October 2009. Follow-up examinations (including 24-hour Holter monitoring) were done 3, 6 and 12 months post-ablation, and yearly thereafter.

Arrhythmia recurrence was recorded when patients reported symptoms of arrhythmia and/or when an atrial tachyarrhythmia (AF, atrial flutter or atrial tachycardia), lasting 30 seconds or longer, was captured on a 12-lead electrocardiogram, event recorder, or Holter monitor recording. Atrial arrhythmias occurring during the two months following the procedure (blanking period) were not counted as recurrences since they do not necessarily imply failure of the procedure. NOTE: 39% of patients had documented arrhythmia during the blanking period, and 80% during the first month following the ablation. However, 40% of ablatees having arrhythmia during the blanking period were free of arrhythmia at the 12-month check-up.

Twelve months post-ablation, 76.2% of study participants were arrhythmia-free without the use of antiarrhythmic drugs (AADs), while 23.8% had experienced one or more arrhythmia episodes, mostly (83%) atrial fibrillation. At the five-year follow-up, 63% of patients having undergone a single procedure were arrhythmia-free without the use of AADs. It is of interest to note that 87% of ablatees who were arrhythmia-free at 12 months were also arrhythmia-free at 44 months. This indicates a highly favourable long-term prognosis for afibbers who are arrhythmia-free at 12 months.

Of the 198 patients experiencing arrhythmia during the first 12 months (early recurrence), 161 (81.3%) underwent repeat ablations which, after an average 14 months of follow-up, were completely successful (no arrhythmia, no AADs) in 78.9% of cases, and partially successful (no arrhythmia, but still taking AADs) in 13.7% of cases. Of the 74 patients experiencing late recurrence (arrhythmia episodes after the 12-month follow-up), 27 underwent a repeat ablation which was completely successful in 74.1% of cases, and partially successful in 25.9% of cases after 17 months of follow-up. At last follow-up (median 55 months from initial ablation), 660 of 785 patients (46 patients were lost to long-term follow-up) were free of arrhythmia without the use of AADs (84%) after a total of 1019 ablations (1.2 per patient). Another 11% was arrhythmia-free with the use of AADs, leaving only 5% failures that were managed with beta- or calcium channel blockers.

The incidence of procedure-related complications was low at 2.4%. and no procedure-related deaths were observed during follow-up. Antiarrhythmic therapy was continued for two months post-ablation, and warfarin was administered for at least one year post-procedure. Among the 587 patients with no arrhythmia recurrence at the 12-month check-up, warfarin was stopped in the 449 patients (76%) with a CHADS2 score of 2 or less, but continued in all patients with a CHADS2 score of 3 or higher. Over a median follow-up of 44 months, only one patient (0.6%) suffered an ischemic stroke, and this had minimal residual deficit. A multivariable Cox proportional hazards analysis showed that early recurrence was associated with older age, higher body mass index, persistent or permanent afib, reduced left ventricular ejection fraction, enlarged left atrium, and high levels of C-reactive protein and BNP (brain natriuretic peptide). Late recurrence, in contrast, was only associated with an enlarged left atrium, and persistent or permanent afib at baseline. The authors conclude that pulmonary vein isolation is safe and efficacious for long-term maintenance of sinus rhythm in patients with drug-resistant atrial fibrillation.

Hussein, AA, Wazni, O, et al. Natural history and long term outcomes of ablated atrial fibrillation. Circulation: Arrhythmia and Electrophysiology, April 14, 2011 [Epub ahead of print]

Editor's Comment: The Cleveland data are a most welcome addition to the information available in regard to the likelihood that an initially successful pulmonary vein isolation (PVI) procedure will still keep an afibber arrhythmia-free for at least five years post-procedure. It is most encouraging to note that 87% of ablatees who were arrhythmia-free at 12 months were also arrhythmia-free at 44 months. This indicates a highly favourable long-term prognosis for afibbers who are arrhythmia-free at 12 months.

We now have five studies providing data on the long-term success of catheter ablation (PVI) in the treatment of atrial fibrillation.

• The San Diego study involved 71 paroxysmal afibbers that underwent an initial PVI procedure at the University of California (San Diego) Medical Center between January 1, 2002 and August 31, 2003 and were followed for a minimum of 5 years. Results were reported in American Journal of Cardiology, Vol. 104, 2009, pp. 366-72
• The afibbers.org 2009 ablation/maze survey involved 88 afibbers (78% paroxysmal) that underwent an initial PVI procedure at various hospitals and clinics between 1997 and 2005 and were followed for up to 10 years. Results were reported in the December 2009/January 2010 issue of The AFIB Report.
• The Hamburg study involved 161 afibbers that underwent an initial PVI procedure at the Asklepios Klinik St. Georg in Hamburg, Germany in 2003 and 2004 and were followed for a median of 4.6 years. Results were reported in Circulation, Vol. 122, 2010, pp. 2368-77
• The Bordeaux study involved 100 afibbers (64% paroxysmal) that underwent an initial PVI procedure at Hopital Cardioloque du Haut Leveque in Bordeaux, France between January 2001 and April 2002 and were followed for a minimum of 5 years. Results were reported in the Journal of the American College of Cardiology, Vol. 57, No. 2, January 11, 2011, pp. 160-66
• The Cleveland study involved 831 afibbers (69% paroxysmal) that underwent an initial PVI procedure at the Cleveland Clinic during 2005 and were followed for 55 months. Results were reported in Circulation: Arrhythmia and Electrophysiology, April 14, 2011 [Epub ahead of print]

* From initial procedure
** From final procedure

The Cleveland data clearly shows the importance of a "blanking" period. Any arrhythmia occurring during this period is ignored in calculating the success for year 1 and subsequent years. In the case of the Cleveland patients, 39% had a documented arrhythmia occurrence during the 2-month blanking period and 80% had one during the first month following the procedure. However, 40% of ablatees experiencing arrhythmia during the blanking period were free of arrhythmia at the 12-month check-up. In the case of the afibbers.org survey, 45% of survey participants had arrhythmia recurrence during the 6-month blanking period following the initial procedure; however, 58% of patients reporting blanking period arrhythmias were arrhythmia-free at the 12-month check-up.

The observance of a blanking period, obviously and rightly so, significantly improves results for both the first and subsequent years. For some unexplained reason the Bordeaux group did not include a blanking period but rather used antiarrhythmics and bisoprolol freely in the event of early arrhythmia occurrences. This may, in large part, explain their rather poor results (40% success at end of first year, 37% at end of 2nd year, and 29% at end of 5th year). The Bordeaux study reveals that the recurrence rate (AF, atrial flutter, and atrial tachycardia) during the first 6 months was 56% and that most recurrences took place in the first month. This means that 56 patients were treated as failures even before the first year success rate was calculated. Had the first 6 months been considered a blanking period rather than an exclusion period, it is likely that 50% of the patients that were excluded from calculating the single procedure success rates would have been afib-free at the first year check-up.

In other words, instead of just 40 ablatees being arrhythmia-free at year 1, it is likely that 40 + (56/2) = 68 would have achieved this status giving a first year success rate of 68%. Following the same logic, the success rate at year 2 would be 65% and that at 5 years 57%. In considering the Bordeaux results it should also be kept in mind that this group treated the highest percentage of persistent, permanent and non-lone afibbers and also found that the recurrence rate for permanent afibbers was twice that observed for paroxysmal and persistent afibbers.

(1) Free of any atrial arrhythmia without the use of antiarrhythmics

In interpreting the Bordeaux results for multiple procedures please note that I was unable to adjust the two and five year results for multiple procedures to reflect the lack of a blanking period. Had I been able to do so the reported success rates would have been higher. Please also note that patients undergoing repeat procedures at the Cleveland Clinic were followed for a maximum of only 17 months rather than 55 months (the follow-up period for the initial procedures). This would tend to exaggerate the success rates for multiple procedures at the 5-year mark. It should also be noted that 44% of participants in the San Diego study underwent repeat procedures with a follow-up period of only 8 months. Finally, the afibbers involved in the 2009 ablation/maze survey (afibbers.org) were followed up for at least 4 years both after their initial and final procedures.

It is clear that the results of the 5 studies are not directly comparable due to the use of different blanking periods and follow-up durations. However, it is probably reasonable to use the results to conclude that the average complete success rates for an initial PVI procedure performed by a highly skilled EP operating at a high-volume center would be about 70% at year 1 and about 55% at year 5.

After multiple procedures the likely 2-year success rate would be around 80% and the 5-year rate about 75%, indicating quite a slow recurrence progression. Our 2009 Ablation/Maze Survey involved 88 AF patients who had undergone their last catheter ablation more than four years ago (53 had only one procedure). The long-term success rate (no atrial arrhythmia and no use of antiarrhythmic drugs) was found to be highly dependent on whether or not the patients had experienced atrial arrhythmias during the last six months of the 12-month period following their last procedure (Index Period). Those who had not experienced arrhythmias during their index period had success rates of 84% at year two, and 86% at year five. In contrast, those patients who did experience arrhythmias during the index period had success rates of only 33% at years two and five. Thus, absence of atrial arrhythmias during the index period is clearly a very important predictor of long-term success. Being a persistent or permanent afibber prior to the procedure was found to be associated with a 5% lower success rate at five years.

In judging the long-term success of catheter ablation for AF, it should also be kept in mind that the failure criteria of one episode lasting 30 seconds or more, is very strict and not really that relevant to an individual AF patient. In our survey we found that at the end of year four, 27% of respondents were still experiencing AF episodes. However, their frequency was down by 95% from pre-procedure levels and the total time spent in AF was down from 7% to 0.2% for paroxysmal afibbers. The reduction in AF burden from pre-procedure days to year four was 97%, and this decline was pretty well universal with only 1 in 16 respondents reporting an increase in burden.