The usual endpoint for clinical trials for catheter ablation of atrial fibrillation (AF) has been the time to first recurrence of an episode of AF lasting for more than 30 seconds.1 This endpoint has been used by trialists, federal approval agencies, and industry for good reason — time to first recurrence is a simple endpoint and can be subjected to Kaplan-Meier analysis to account for variable durations of follow-up. However, it unfortunately does not tell the whole story. There are many patients with paroxysmal AF who have episodes that last hours every day, and patients with persistent AF who undergo an ablation procedure that results in virtual elimination of their episodes. Nevertheless, if these patients have a single AF episode lasting for more than 30 seconds that is captured on a monitoring device, they are categorized in a clinical trial as a failure. Success rates of 50-70% in ablation trials send the wrong message about efficacy to patients and referring cardiologists. And after the recent negative results from the CABANA study2, there has been much negative commentary related to AF ablation.
The redo rate is a reasonable endpoint to consider if one is interested in knowing how many patients continue to have AF after an initial ablation procedure that is sufficiently bothersome enough to undergo a repeat procedure. In the recently published STOP AF Post-Approval Study3, the recurrence rate at three years after cryoablation was 36%, but the redo rate was only 20%. Quality of life (QOL) is another way to look at benefit. Two recent studies demonstrated that QOL improves after ablation for AF4-5, but it is a relatively insensitive way to detect benefit from the procedure.
Ideally, comparing the frequency and duration of AF before and after ablation would be the best endpoint. However, measuring AF burden requires continuous monitoring, typically with an implantable loop recorder or other cardiac implantable electrical device, and requires intensive data collection and analysis. At EHRA 2019, Dr. Jason Andrade presented the results of the CIRCA-DOSE study, which evaluated the cryoballoon vs the irrigated radiofrequency (RF) catheter ablation for AF.6 Investigators compared three ablation strategies in patients with AF. The AF was paroxysmal in over 90%. Patients underwent pulmonary vein isolation using either RF ablation with contact force, or using cryoballoon ablation with one of two dosing regimens: a minimum of a single four-minute freeze or a minimum of two separate two-minute freezes. Unlike the FIRE AND ICE study7, radiofrequency ablation was performed with modern contact force ablation catheters in all patients, and the cryoballoon ablation procedures were performed with newer second-generation balloons in all patients. Also, unlike the FIRE AND ICE study, the CIRCA-DOSE study looked at two different dosing regimens of the cryoballoon based on findings from earlier animal studies showing that shorter freezes may be as effective. The primary endpoint was freedom from any atrial arrhythmia at 12-month follow-up after a single ablation procedure excluding a three-month blanking period. The success rate was about 52% in each group and there was no significant difference in the three treatment arms. Cryoballoon ablation was associated with shorter procedure times, particularly in the two-minute freeze group, but a higher fluoroscopy time. It will be important to also learn if there was a difference in the patient experience during the three-month period immediately after the procedure. One of the most interesting findings from the study, however, was the impact of ablation on the arrhythmia burden. The median baseline AF burden ranged from 1.6-3.7% in the three groups, and the median reduction after ablation in the AF burden compared to baseline in all groups was nearly 99%, with no significant difference between groups. There are very few therapies in medicine that reduce the burden of a problem by 99%.
Catheter ablation for AF is highly effective. Calls for trials using a sham control are misguided. The messages to patients and cardiologists should not be that the success rate for ablation is 50-70%, and that it has no effect on mortality. The message should be that catheter ablation in appropriately selected patients with symptomatic paroxysmal AF results in a 99% reduction in AF burden.
Visit us at Heart Rhythm 2019! Dr. Knight will be available at the EPLD booth (#2229) on May 10th from 10-10:30 AM. Come say hello — we’ll see you there!
- Calkins H, et al. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation. Heart Rhythm. 2017;14(10):e275-e444. doi.org/10.1016/j.hrthm.2017.07.009.
- Packer DL, Mark DB, Robb RA, et al. Effect of catheter ablation vs antiarrhythmic drug therapy on mortality, stroke, bleeding, and cardiac arrest among patients with atrial fibrillation. JAMA. 2019;321(13):1261-1274. doi:10.1001/jama.2019.0693.
- Knight BP, Novak PG, Sangrigoli R, et al. Long-term outcomes after ablation for paroxysmal atrial fibrillation using the second-generation cryoballoon: final results from STOP AF Post-Approval Study. JACC Clin Electrophysiol. 2019;5(3):306-314. doi.org/10.1016/j.jacep.2018.11.006.
- Mark DB, Anstrom KL, Sheng S, et al. Effect of catheter ablation vs medical therapy on quality of life among patients with atrial fibrillation: the CABANA randomized clinical trial. JAMA. 2019;321(13):1275-1285. doi:10.1001/jama.2019.0692.
- Effect of catheter ablation vs antiarrhythmic medication on quality of life in patients with atrial fibrillation: the CAPTAF randomized clinical trial. JAMA. 2019;321(11):1059-1068. doi:10.1001/jama.2019.0335.
- Andrade JG, Champagne J, Dubuc M, et al. A randomized clinical trial of cryoballoon vs. irrigated radiofrequency catheter ablation for atrial fibrillation: the CIRCA-DOSE study. Presented at the European Heart Rhythm Association Annual Congress March 2019.
- Kuck KH, Brugada J, Fürnkranz A, et al. Cryoballoon or radiofrequency ablation for paroxysmal atrial fibrillation. N Engl J Med. 2016;374:2235-2245. doi:10.1056/NEJMoa1602014.