Accurate discrimination between persistent and long-standing AF based on standard surface recordings was demonstrated. This information could contribute to optimize the management of sustained AF, permitting appropriate therapeutic decisions and thereby providing substantial clinical cost savings.

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Key pointsr Beat-to-beat alternation (alternans) of the cardiac action potential duration is known to precipitate life-threatening arrhythmias and can be driven by the kinetics of voltage-gated membrane currents or by instabilities in intracellular calcium fluxes.r To prevent alternans and associated arrhythmias, suitable markers must be developed to quantify the susceptibility to alternans; previous theoretical studies showed that the eigenvalue of the alternating eigenmode represents an ideal marker of alternans.r Using rabbit ventricular myocytes, we show that this eigenvalue can be estimated in practice by pacing these cells at intervals varying stochastically.r We also show that stochastic pacing permits the estimation of further markers distinguishing between voltage-driven and calcium-driven alternans.r Our study opens the perspective to use stochastic pacing during clinical investigations and in patients with implanted pacing devices to determine the susceptibility to, and the type of alternans, which are both important to guide preventive or therapeutic measures.Abstract Alternans of the cardiac action potential (AP) duration (APD) is a well-known arrhythmogenic mechanism. APD depends on several preceding diastolic intervals (DIs) and APDs, which complicates the prediction of alternans. Previous theoretical studies pinpointed a marker called λ alt that directly quantifies how an alternating perturbation persists over successive APs. When the propensity to alternans increases, λ alt decreases from 0 to -1. Our aim was to quantify λ alt experimentally using stochastic pacing and to examine whether stochastic pacing allows discriminating between voltage-driven and Ca 2+ -driven alternans. APs were recorded in rabbit ventricular myocytes paced at cycle lengths (CLs) decreasing progressively and incorporating stochastic variations. Fitting APD with a function of two previous APDs and CLs permitted us to estimate λ alt along with additional markers characterizing whether the dependence of APD on previous DIs or CLs is strong (typical for voltage-driven alternans) or weak (Ca 2+ -driven alternans). During the recordings, λ alt gradually decreased from around 0 towards -1. Intermittent alternans appeared when λ alt reached -0.8 and was followed by sustained alternans. The additional markers detected that alternans was Ca 2+ driven in control experiments and voltage driven in the presence of ryanodine. This distinction could be made even before alternans was manifest (specificity/sensitivity >80% for -0.4 > λ alt > -0.5). These observations were confirmed in a mathematical model of a rabbit ventricular myocyte. In conclusion, stochastic pacing allows the practical estimation of λ alt to reveal the onset of alternans and distinguishes between voltage-driven and Ca 2+ -driven mechanisms, which is important since these two mechanisms may precipitate arrhythmias in different manners.

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Aims Experimental models have reported conflicting results regarding the role of dispersion of repolarization in promoting atrial fibrillation (AF). Repolarization alternans, a beat-to-beat alternation in action potential duration, enhances dispersion of repolarization when propagation velocity is involved. Methods and results In this work, original electrophysiological parameters were analysed to study AF susceptibility in a chronic sheep model of pacing-induced AF. Two pacemakers were implanted, each with a single right atrial lead. Right atrial depolarization and repolarization waves were documented at 2-week intervals. A significant and gradual decrease in the propagation velocity at all pacing rates and in the right atrial effective refractory period (ERP) was observed during the weeks of burst pacing before sustained AF developed when compared with baseline conditions. Right atrial repolarization alternans was observed, but because of the development of 2/1 atrioventricular block with far-field ventricular interference, its threshold could not be precisely measured. Non-sustained AF was not observed at baseline, but appeared during the electrical remodelling in association with a decrease in both ERP and propagation velocity. Conclusion We report here on the feasibility of measuring ERP, atrial repolarization alternans, and propagation velocity kinetics and their potential in predicting susceptibility to AF in a free-behaving model of pacing-induced AF using the standard pacemaker technology.