Ibutilide increases the variability and complexity of atrial fibrillation electrograms: antiarrhythmic insights using signal analyses

Abstract

Introduction: Intravenous ibutilide is used to convert atrial fibrillation (AF) to sinus rhythm (SR) due to its Class III antiarrhythmic mechanisms. However, the effects of ibutilide on local electrograms (EGMs) during AF have not been elucidated.

Methods and results: We used EGM analysis techniques to characterize how ibutilide administration changes the frequency, morphology, and repeatability of AF EGM signals, thereby providing insight into ibutilide's antiarrhythmic mechanism of action. AF recordings were collected from 21 patients with AF, both before and after ibutilide administration. The effects of ibutilide on the following AF EGM parameters were assessed: (1) dominant frequency (DF), (2) variations in EGM amplitude and overall morphology, (3) repetition of EGM patterns, and (4) complexity of the AF frequency spectra. When comparing pre- versus post-ibutilide administration EGMs, DF decreased from 5.45 Hz to 4.02 Hz (P < 0.0001). There was an increase in the variability of both AF EGM amplitudes (P = 0.003) and overall AF EGM morphologies (P = 0.003). AF EGM pattern repetitiveness decreased (P = 0.01), and the AF frequency spectral profile manifested greater complexity (P = 0.02).

Conclusions: Novel EGM signal analysis techniques reveal that ibutilide administration causes increased complexity in the atrial electrical activation pattern with decreasing rate. These findings may be explained by the progressive destabilization of higher frequency, more homogeneous primary drivers of AF over the course of ibutilide administration, and/or less uniform propagation of atrial activation, until AF maintenance becomes more difficult and either transforms to atrial tachycardia or terminates to SR.

Keywords: atrial fibrillation; dominant frequency; electrogram analysis; ibutilide; linear prediction.

Figure 1

Protocol for EGM sampling in AF patients before and after ibutilide administration.

Figure 2

Example of the use of linear spectral analysis to calculate the normalized magnitude of the dominant frequency and the mean of the power spectrum in a representative patient comparing pre-ibutilide (A) vs. post-ibutilide (B) infusion patients. After ibutilide (B), the dominant frequency (black dots) decreases from 7.0 to 4.5 Herz, while the mean of the normalized power spectrum (solid lines) rises from 0.33 to 0.38, indicating more disparate, lower frequency sources contributing to the frequency power spectrum.

Figure 3

Comparison of the change in the magnitude of the dominant frequency amplitude of the power spectrum in pre-ibutilide (A) vs. post-ibutilide (B) AF patients. EGMs manifest lower dominant frequency amplitudes post-ibutilide, consistent with less contribution to the power spectrum by a more stable, dominant source, as well as more complexity in their frequency spectra post-ibutilide, manifested by higher means of the normalized power spectrum, consistent with AF frequencies due to more disparate sources of activation.

Figure 3

Comparison of the change in the magnitude of the dominant frequency amplitude of the power spectrum in pre-ibutilide (A) vs. post-ibutilide (B) AF patients. EGMs manifest lower dominant frequency amplitudes post-ibutilide, consistent with less contribution to the power spectrum by a more stable, dominant source, as well as more complexity in their frequency spectra post-ibutilide, manifested by higher means of the normalized power spectrum, consistent with AF frequencies due to more disparate sources of activation.

Figure 4

Example of phase plot method used to measure the variation of amplitudes in an AF EGM signal. Pre-ibutilide EGMs (A) possess phase plots with more overlapped amplitude points (B) than the phase plots (D) of post-ibutilide EGMs (C), indicating more variation in AF EGM amplitudes post-ibutilide infusion.

Figure 5

Comparison of coefficient of variation for EGM amplitudes collected pre-ibutilide vs. post-ibutilide. EGM amplitudes become more variable post-ibutilide.

Figure 6

Graph of mean sum of absolute values of EGM morphologies in pre- vs. post-ibutilide EGM collections. A lower magnitude implies more variation of overall EGM morphologies.

Figure 7

Graph of linear prediction error of EGMs collected pre-ibutilide vs. post-ibutilide. More reproducible EGM patterns, consistent with less complex EGMS, were present in patients before ibutilide was given.