Human Atrial Fibrillation Drivers Resolved With Integrated Functional and Structural Imaging to Benefit Clinical Mapping.

OBJECTIVES: This study sought to improve atrial fibrillation (AF) driver identification by integrating clinical multielectrode mapping with driver fingerprints defined by high-resolution ex vivo 3-dimensional (3D) functional and structural imaging. BACKGROUND: Clinical multielectrode mapping of AF drivers suffers from variable contact, signal processing, and structural complexity within the 3D human atrial wall, raising questions on the validity of such drivers. METHODS: Sustained AF was mapped in coronary-perfused explanted human hearts (n = 11) with transmural near-infrared optical mapping (∼0.3 mm2 resolution). Simultaneously, custom FIRMap catheters (∼9 × 9 mm2 resolution) mapped endocardial and epicardial surfaces, which were analyzed by Focal Impulse and Rotor Mapping activation and Rotational Activity Profile (Abbott Labs, Chicago, Illinois). Functional maps were integrated with contrast-enhanced cardiac magnetic resonance imaging (∼0.1 mm3 resolution) analysis of 3D fibrosis architecture. RESULTS: During sustained AF, near-infrared optical mapping identified 1 to 2 intramural, spatially stable re-entrant AF drivers per heart. Driver targeted ablation affecting 2.2 ± 1.1% of the atrial surface terminated and prevented AF. Driver regions had significantly higher phase singularity density and dominant frequency than neighboring nondriver regions. Focal Impulse and Rotor Mapping had 80% sensitivity to near-infrared optical mapping-defined driver locations (16 of 20), and matched 14 of 20 driver visualizations: 10 of 14 re-entries seen with Rotational Activity Profile; and 4 of 6 breakthrough/focal patterns. Focal Impulse and Rotor Mapping detected 1.1 ± 0.9 false-positive rotational activity profiles per recording, but these regions had lower intramural contrast-enhanced cardiac magnetic resonance imaging fibrosis than did driver regions (14.9 ± 7.9% vs. 23.2 ± 10.5%; p < 0.005). CONCLUSIONS: The study revealed that both re-entrant and breakthrough/focal AF driver patterns visualized by surface-only clinical multielectrodes can represent projections of 3D intramural microanatomic re-entries. Integration of multielectrode mapping and 3D fibrosis analysis may enhance AF driver detection, thereby improving the efficacy of driver-targeted ablation.