Phase- and Frequency-Domain Analysis of the Surface ECG Localizes Arrhythmogenic Sources of Ventricular Fibrillation in Humans

Abstract

<h3>Background</h3> Ventricular fibrillation (VF) has been proposed to be maintained by localized high-frequency sources. We tested the hypothesis that combined spectral and nonlinear analyses of the standard ECG enables accurate localization of VF sources. <h3>Methods</h3> Six precordial ECG leads were used to record from 10 ischemic cardiomyopathy (IC) and 15 Brugada syndrome (BrS; type 1 ECG) patients during VF. Fourier and Hilbert transforms of ECG waveforms were used for frequency and phase analyses, respectively. <h3>Results</h3> Despite temporal variability, induced VF episodes recorded for 19.9 ± 8.6 seconds displayed long-lasting periods (7.8 ± 2.1 seconds [range 4.9–12.8 seconds]) of spectral power at a common frequency (shared frequency [SF]) in all leads (5.9 ± 0.8 Hz). In BrS patients, phase analysis of the SF showed a V₁–V₆ activation sequence as would be expected from waves originating at the base of the ventricles in patients displaying a type 1 ECG pattern (Friedman <i>P</i> <.001). Hilbert-based phase comparison confirmed that the V₁–V₆ sequence was the most stable over the whole VF duration. However, phase analysis of the SF in IC patients with anteroseptal (n = 4), apex (2), and lateral (4) myocardial infarction displayed activation at V₁–V₂, V₃–V₄, and V₅–V₆ as the earliest, respectively, consistent with an activation originating from the scar location (<i>P</i> <.01). The observed patterns correlated with the more stable sequence observed during Hilbert-based phase analysis (<i>P</i> <.05). Paired comparison showed that phase sequences were similar during monomorphic ventricular tachycardia and VF (Pearson coefficient 0.58, <i>P</i> <.001). Also, a dominant frequency gradient was observed between precordial leads corresponding to the scar region and the contralateral leads (5.86 ± 0.9 Hz vs 5.44 ± 1.1 Hz; paired <i>t</i>-test <i>P</i> = .011). <h3>Conclusions</h3> Early VF in BrS and IC patients is characterized by a steady sequence in the phase-frequency domain consistent with anatomic location of the arrhythmogenic substrate. These results are consistent with the prediction that VF is maintained by a small number of high-frequency sources that interact with the surrounding myocardium to generate fibrillatory conduction.