RADAR: A Multicenter Food and Drug Administration Investigational Device Exemption Clinical Trial of Persistent Atrial Fibrillation

Abstract

Background: Pulmonary vein isolation is insufficient to treat all patients with persistent atrial fibrillation (AF), and effective adjunctive ablation strategies are needed. Ablation of AF drivers holds promise, but current technologies to identify drivers are limited by spatial resolution. In a single-arm, first-in-human, investigator-initiated Food and Drug Administration Investigational Device Exemption study, we used a novel system for real-time, high-resolution identification of AF drivers in persistent AF.

Methods: Patients with persistent or long-standing persistent AF underwent ablation using the RADAR (Real-Time Electrogram Analysis for Drivers of Atrial Fibrillation) system in conjunction with a standard electroanatomical mapping system. After pulmonary vein isolation, electrogram and spatial information was streamed to the RADAR system and analyzed to identify driver domains to target for ablation.

Results: Across 4 centers, 64 subjects were enrolled: 73% male, age, 64.7±9.5 years; body mass index, 31.7±6.0 kg/m2; left atrium size, 54±10 mm, with persistent/long-standing persistent AF in 53 (83%)/11 (17%), prior AF ablation (re-do group) in 26 (41%). After 12.6±0.8 months follow-up, 68% remained AF-free off all antiarrhythmics; 74% remained AF-free and 66% remained AF/atrial tachycardia/atrial flutter-free on or off AADs (antiarrhythmic drugs). AF terminated with ablation in 35 patients (55%) overall and in 23/38 (61%) of de novo ablation patients. For patients with AF termination during ablation, 82% remained AF-free and 74% AF/atrial tachycardia/atrial flutter-free during follow-up on or off AADs. Patients undergoing first-time ablation generally had higher rates of freedom from AF than the re-do group.

Conclusions: This novel technology for panoramic mapping of AF drivers showed promising results in a persistent/long-standing persistent AF population. These data provide the scientific basis for a randomized trial.

Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03263702; IDE#G170049.

Keywords: ablation; atrial fibrillation; follow-up; human; pulmonary vein.

Figures

Figure 1.

Conceptual basis of RADAR (Real-Time Electrogram Analysis for Drivers of Atrial Fibrillation) mapping. A, Signals are collected simultaneously from the coronary sinus (CS) and mapping catheters for 20 s at each different location within the atrium (circle, square, triangle, hexagon). B, Repetitive activation patterns (green, yellow, red, blue, purple) are identified from the recorded CS electrograms. Each pattern defines a phase of atrial fibrillation. C, Local atrial activation is extracted from the recorded data at each location and stitched together to create panoramic conduction vector maps for each phase. This process is repeated for each phase (green, yellow, red, blue) with the associated local atrial activation data. Sites of rotational activity (R) and focal impulses (F) are tagged.

Figure 2.

Processed unipolar signals. Three separate processed recordings are shown from the coronary sinus (A–C) and circular mapping (D–F) catheters in red, green, and blue. These signals are overlaid and shown in different coronary sinus (CS) phases (green, yellow) and for different mapping catheter positions (triangle, square). The preservation of remote atrial activation during specific CS activation patterns is illustrated by the overlapping signals on the mapping catheter at different time points and locations.

Figure 3.

Creation of probabilistic atrial driver assessment (PADA) map. High-density electrogram, voltage, and location information are collected throughout the left atrium (LA) using standard mapping equipment (A). Individual conduction vector maps for each phase (B) are combined to yield a driver density map (C). A voltage map collected during atrial fibrillation (AF; D) is incorporated with this information to output the PADA map (E). AF was successfully terminated with ablation (red and white dots) at the highlighted driver doman on the posterior wall in this patient with long-standing persistent AF for 12 y.

Figure 4.

Flow of information between systems. Catheter location and electrogram data are collected from the mapping catheter and coronary sinus (CS) catheter via a standard mapping system. These data are streamed via a direct connection from the mapping system to a computer running the RADAR (Real-Time Electrogram Analysis for Drivers of Atrial Fibrillation) software for analysis.

Figure 5.

Driver characteristics. The study population had an average of 3.9 left atrial drivers identified. The distribution of left atrial drivers is shown: rotational sources are shown as red circles, while focal impulses are shown as blue stars. LA indicates left atrium; and RA, right atrium.

Figure 6.

Kaplan-Meier estimates of single-procedure freedom from atrial fibrillation (AF). Shown are the curves for the full cohort (blue line), the de novo-alone group (red line), and the re-do group (green line) without the use of antiarrhythmic drugs (top), and with the addition of antiarrhythmic drugs (bottom). Three patients were withdrawn with no follow-up and 4 patients were lost with partial follow-up. Statistical analysis with censoring was performed accordingly, using Minitab 19 software. AAD indicates antiarrhythmic drug.