Treatment of atrial fibrillation by the ablation of localized sources: CONFIRM (Conventional Ablation for Atrial Fibrillation With or Without Focal Impulse and Rotor Modulation) trial

Abstract

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).

Conflict of interest statement

Disclosures: 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 reports having received honoraria from Medtronic, St. Jude Medical, and Biotronik. Dr. Miller reports having received honoraria from Medtronic, St. Jude Medical, Biotronik, Biosense-Webster, Boston Scientific and is a scientific advisor to Topera. Dr. Shivkumar is a scientific advisor to Topera. Dr. Krummen and Mr. Clopton report no conflicts.

Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1. Computational Mapping of ‘Electrical Rotor’ During Atrial Fibrillation

(A) Electrocardiogram and intracardiac signals in an 85 year old man during paroxysmal AF. (B) Fluoroscopy shows a 64 pole catheter in each atrium, an implanted continuous ECG monitor, diagnostic catheters in the coronary sinus and left atrium and an esophageal temperature probe at the inferior left atrium. (C) Left Atrial Rotor During AF, showing clockwise revolution (coded red to blue based on activation time scale) around a precessing center for 3 cycles (AF1–AF3; see Supplemental Movie 1). The right atrium depicts the superior and inferior vena cavae above and below, and lateral and medial tricuspid annuli at left and right. The left atrium depicts superior and inferior mitral annuli above and below, and pulmonary vein pairs. Electrode are labeled A–H and 1–8, respectively. (D) Computationally Processed and Filtered intracardiac signals show sequential activation over the rotor path for cycles AF1–AF3 (arrowed). FIRM ablation at this rotor terminated AF to sinus rhythm in < 1 minute (Supplemental movies 2–3).

Figure 2. Acute Termination of Atrial Fibrillation to Sinus Rhythm By Focal Impulse and Rotor Modulation (FIRM) Ablation

(A) Left atrial rotor with counterclockwise activation (red to blue) and disorganized right atrium during AF in a 60 year old man. (B) FIRM ablation at left atrial rotor terminated AF to sinus rhythm in < 1 minute, with ablation artifact recorded at rotor center. The patient is AF-free on implanted cardiac monitor at > 1 year. Scale bars 1 cm, 1 second; CS: coronary sinus electrogram. Atrial orientations as in figure 1.

Figure 3. Acute Termination of AF (two sources) to Sinus Rhythm By FIRM Ablation

(A) Right atrial rotor (clockwise) and simultaneous left atrial focal impulse (arrowed) during persistent AF in a 47 year old man. (B) FIRM ablation at right atrial rotor terminated AF to sinus rhythm in 5.5 minutes (see Supplemental movies 4–5). Note the slowing of AF rate during ablation. The left atrial focal impulse source was also treated by FIRM ablation. The patient is AF-free on implanted cardiac monitor at > 1 year. Scale bars 1 cm, 1 second; CS: coronary sinus electrogram. Atrial orientations as in figure 1.

Figure 4. Cumulative freedom from the Primary End Point (atrial fibrillation), in all cases and those at first ablation

(A) For All cases; (B) Patients off Anti-Arrhythmic Medications. Intention-to-Treat Analysis, and p-values reflect the complete followup period.