Author + information
- Received May 29, 2012
- Accepted May 29, 2012
- Published online August 14, 2012.
- Sanjiv M. Narayan, MD, PhD⁎,†,⁎ (, )
- David E. Krummen, MD⁎,†,
- Kalyanam Shivkumar, MD, PhD‡,
- Paul Clopton, MS†,
- Wouter-Jan Rappel, PhD§ and
- John M. Miller, MD∥
- ↵⁎Reprint requests and correspondence:
Dr. Sanjiv M. Narayan, Cardiology/111A, University of California, 3350 La Jolla Village Drive, San Diego, California 92161
Objectives We hypothesized that human atrial fibrillation (AF) may be sustained by localized sources (electrical rotors and focal impulses), whose elimination (focal impulse and rotor modulation [FIRM]) may improve outcome from AF ablation.
Background Catheter ablation for AF is a promising therapy, whose success is limited in part by uncertainty in the mechanisms that sustain AF. We developed a computational approach to map whether AF is sustained by several meandering waves (the prevailing hypothesis) or localized sources, then prospectively tested whether targeting patient-specific mechanisms revealed by mapping would improve AF ablation outcome.
Methods We recruited 92 subjects during 107 consecutive ablation procedures for paroxysmal or persistent (72%) AF. Cases were prospectively treated, in a 2-arm 1:2 design, by ablation at sources (FIRM-guided) followed by conventional ablation (n = 36), or conventional ablation alone (n = 71; FIRM-blinded).
Results Localized rotors or focal impulses were detected in 98 (97%) of 101 cases with sustained AF, each exhibiting 2.1 ± 1.0 sources. The acute endpoint (AF termination or consistent slowing) was achieved in 86% of FIRM-guided cases versus 20% of FIRM-blinded cases (p < 0.001). FIRM ablation alone at the primary source terminated AF in a median 2.5 min (interquartile range: 1.0 to 3.1 min). Total ablation time did not differ between groups (57.8 ± 22.8 min vs. 52.1 ± 17.8 min, p = 0.16). During a median 273 days (interquartile range: 132 to 681 days) after a single procedure, FIRM-guided cases had higher freedom from AF (82.4% vs. 44.9%; p < 0.001) after a single procedure than FIRM-blinded cases with rigorous, often implanted, electrocardiography monitoring. Adverse events did not differ between groups.
Conclusions Localized electrical rotors and focal impulse sources are prevalent sustaining mechanisms for human AF. FIRM ablation at patient-specific sources acutely terminated or slowed AF, and improved outcome. These results offer a novel mechanistic framework and treatment paradigm for AF. (Conventional Ablation for Atrial Fibrillation With or Without Focal Impulse and Rotor Modulation [CONFIRM]; NCT01008722)
This work was supported by grants to Dr. Narayan from the National Institutes of Health (HL70529, HL83359, HL83359-S1) and from the Doris Duke Charitable Foundation. Drs. Narayan and Rappel are authors of intellectual property owned by the University of California Regents and licensed to Topera Inc. Topera does not sponsor any research, including that presented here. Dr. Narayan holds equity in Topera, and has received honoraria from Medtronic, St. Jude Medical, and Biotronik. Dr. Miller has received honoraria from Medtronic, St. Jude Medical, Biotronik, Biosense-Webster, Boston Scientific, and Topera. Dr. Shivkumar is an unpaid scientific advisor to Topera. Dr. Krummen and Mr. Clopton have reported they have no relationships relevant to the contents of this paper to disclose. Bruce D. Lindsay, M.D., served as Guest Editor for this paper.
- Received May 29, 2012.
- Accepted May 29, 2012.
- American College of Cardiology Foundation