A class of Monte-Carlo-based statistical algorithms for efficient detection of repolarization alternans.

Cardiac repolarization alternans is an electrophysiologic condition identified by a beat-to-beat fluctuation in action potential waveform. It has been mechanistically linked to instances of T-wave alternans, a clinically defined ECG alternation in T-wave morphology, and associated with the onset of cardiac reentry and sudden cardiac death. Many alternans detection algorithms have been proposed in the past, but the majority have been designed specifically for use with T-wave alternans. Action potential duration (APD) signals obtained from experiments (especially those derived from optical mapping) possess unique characteristics, which requires the development and use of a more appropriate alternans detection method. In this paper, we present a new class of algorithms, based on the Monte Carlo method, for the detection and quantitative measurement of alternans. Specifically, we derive a set of algorithms (one an analytical and more efficient version of the other) and compare its performance with the standard spectral method and the generalized likelihood ratio test algorithm using synthetic APD sequences and optical mapping data obtained from an alternans control experiment. We demonstrate the benefits of the new algorithm in the presence of Gaussian and Laplacian noise and frame-shift errors. The proposed algorithms are well suited for experimental applications, and furthermore, have low complexity and are implementable using fixed-point arithmetic, enabling potential use with implantable cardiac devices.

Control of action potential duration alternans in canine cardiac ventricular tissue.

Cardiac electrical alternans, characterized by a beat-to-beat alternation in action potential waveform, is a naturally occurring phenomenon, which can occur at sufficiently fast pacing rates. Its presence has been putatively linked to the onset of cardiac reentry, which is a precursor to ventricular fibrillation. Previous studies have shown that closed-loop alternans control techniques that apply a succession of externally administered cycle perturbations at a single site provide limited spatially-extended alternans elimination in sufficiently large cardiac substrates. However, detailed experimental investigations into the spatial dynamics of alternans control have been restricted to Purkinje fiber studies. A complete understanding of alternans control in the more clinically relevant ventricular tissue is needed. In this paper, we study the spatial dynamics of alternans and alternans control in arterially perfused canine right ventricular preparations using an optical mapping system capable of high-resolution fluorescence imaging. Specifically, we quantify the spatial efficacy of alternans control along 2.5 cm of tissue, focusing on differences in spatial control between different subregions of tissue. We demonstrate effective control of spatially-extended alternans up to 2.0 cm, with control efficacy attenuating as a function of distance. Our results provide a basis for future investigations into electrode-based control interventions of alternans in cardiac tissue.