Non-invasive identification of stable rotors and focal sources for human atrial fibrillation: mechanistic classification of atrial fibrillation from the electrocardiogram

AIMS: To develop electrocardiogram (ECG) tools to quantify the number of sources for atrial fibrillation (AF), i.e. spatially stable rotors and focal impulses, and whether they lie in right or left atrium. Intracardiac mapping has recently shown that paroxysmal and persistent AF is sustained by rotors or focal sources that are stable in location and thus targets for limited ablation [focal impulse and rotor modulation (FIRM)] to eliminate AF. Importantly, the numbers and locations of concurrent sources determine both the complexity of AF and the approach for ablation. METHODS AND RESULTS: In 36 AF patients (n = 29 persistent, 63 ± 9 years) in the CONventional ablation with or without Focal Impulse and Rotor Modulation (CONFIRM) trial, we developed phase lock (PL) to quantify spatial repeatability of ECG 'F-waves' between leads over time. Phase lock spectrally quantifies the angle θ between F-wave voltages in planes formed by ECG leads I, aVF, and V1 at successive points in time. We compared PL with ECG spectral dominant frequency (DF) and organizational index (OI) to characterize stable rotors and focal sources validated by intracardiac FIRM mapping. Focal impulse and rotor modulation ablation alone at ≤3 sources acutely terminated and rendered AF non-inducible or substantially slowed AF in 31 of 36 patients. Receiver operating characteristics of PL for this endpoint had area under the curve (AUC) = 0.72, and the optimum cut-point (PL = 0.09) had 74% sensitivity, 92% positive predictive value (PPV). Receiver operating characteristics areas for OI and DF were 0.50 and 0.58, respectively. Left (n = 28) or right (n = 3) atrial sources were localized by PL with AUC = 0.85, sensitivity 100%, PPV 30%, and negative predictive value 100%. Spectral DF provided AUC = 0.79. Notably, PL did not comigrate with diagnosis of paroxysmal or persistent AF (P = NS), unlike ECG DF. CONCLUSION: The novel metric of ECG PL identifies patients with fewer (≤3) or greater numbers of stable rotors/focal sources for AF, validated by intracardiac FIRM mapping, and localized them to right or left atria. These data open the possibility of using 12-lead ECG analyses to classify AF mechanistically and plan procedures for right- or left-sided FIRM ablation.