The AV synchrogram: A novel approach to quantify atrioventricular coupling during atrial arrhythmias

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Abstract

The generation of ventricular response during atrial arrhythmias and its dependence on atrial activity is poorly understood. This paper introduces the atrioventricular (AV) synchrogram, a novel method for the beat-to-beat assessment of AV coupling during atrial arrhythmias, based on the stroboscopic observation of the ventricular phase at times triggered by atrial activation. The method was applied on a database of 120 atrial electrograms and ECG signals recorded in patients during typical atrial flutter (AFL), rapid atrial flutter (rAFL), and atrial fibrillation (AF). Synchronized epochs of different n:m order were automatically detected in the AV synchrogram and characterized in terms of percentage of significantly coupled beats (plb), maximal length of coupling segments (lmax), average conduction ratio (CR). Synchrogram analysis demonstrated that AV coupling and degree of conduction were significantly affected by the rate and regularity of atrial activity. The occurrence and stability of AV coupled epochs was maximal during regular atrial activation in AFL (median (interquartile range) of plb = 100 (100–100)%, lmax = 29.0 (28.5–29.4) s), and significantly (p < 0.001) decreased at faster atrial rates in rAFL (plb = 74.3 (57.6–100)%, lmax = 7.4 (3.9–28.7) s). A further decrease of coupling indexes occurred at higher irregularity of atrial activity in AF (plb = 25.7 (19.9–30.2)%, lmax = 2.1 (1.8–2.6) s). The increase of atrial rate led to a significant (p < 0.001) reduction of CRs from 0.50 (0.29–0.50) in AFL to 0.25 (0.22–0.25) in rAFL and 0.30 (0.24–0.35) in AF. Application of the analysis to the time course of AF showed the presence of a Farey sequence structure in n:m coupling patterns at increasing atrial rate, which was consistent with the scaling effect of nodal recovery on atrial beats. In conclusion, AV synchrogram analysis enables beat-to-beat assessment of AV coupling and dynamical tracking of AV response during atrial arrhythmias, which may favor mechanistic insight about the genesis of ventricular rhythms and potentially the development of efficacious rate control strategies.

Highlights

► The generation of ventricular response during atrial arrhythmias is poorly understood. ► The AV synchrogram is introduced, which quantifies AV coupling by a stroboscopic observation of the ventricular phase at times triggered by atrial activation. ► AV synchrogram analysis detected changes in AV coupling in different arrhythmia types. ► AV synchrogram analysis reconstructed the dynamics of nodal response during AF time course. ► AV synchrograms may find application for AV node response characterization in the clinical setting.

Introduction

Despite the importance of rate control as a treatment option for atrial arrhythmias, such as atrial flutter and atrial fibrillation (AF), in the acute setting, the mechanisms of atrioventricular (AV) conduction and the genesis of ventricular response during atrial arrhythmias are poorly understood [1].

During atrial arrhythmias, the AV node plays a crucial filtering role, impeding high-frequency atrial activity from reaching the ventricles thereby inducing life-threatening ventricular arrhythmias. The specific rate and time-dependent recovery properties of the AV node determine conduction delay and lead to dropped beats, resulting in a variety of rate-dependent AV block patterns [2], [3], [4]. AV response at high atrial rates is further conditioned by concealed conduction of blocked beats and dual pathway physiology [3], [5], [6], which may give rise to phasic summation and annihilation of atrial inputs [7], adding complexity to the resultant ventricular output.

Although nodal properties and conduction mechanisms can be investigated by specific stimulation protocols [2], [8], these properties are not routinely evaluated in clinical practice, nor determined under spontaneous arrhythmic conditions. An indirect estimation of nodal properties during atrial arrhythmias has been mostly attempted by analyzing the statistical properties of the ventricular interbeat interval (RR) series [9], [10], [11], [12], [13], [14], [15]. The histographic analysis of RR series during AF revealed the presence of different populations of more probable RR intervals, which have been correlated with the existence of preferential intranodal pathways and successful AV node modification [11], [13], [15]. Dependencies between successive RR intervals have been pointed out by Poincarè plot analysis [10], where the presence of interval clusters has been associated with the effectiveness of electrical cardioversion [14]. These results provide evidence that ventricular activation process in AF is not completely random and somehow reflective of the nodal electrophysiological properties. However there are still controversies about the actual electrophysiological meaning of the proposed indexes [16]. As well mechanistic insights on nodal conduction based on RR series analysis are limited by the lack of information on atrial activity.

Experimental [7], [17] and clinical [18], [19] evidence has pointed out the crucial role of the atrial input in the generation of ventricular response during atrial arrhythmias. Clinical studies in patients with AF have suggested that the ventricular response in AF may reflect the irregularity inherent in the atrial activity [19], or, in some cases, RR intervals may be multiples of the dominant atrial cycle length [18]. These results suggest that a careful evaluation of the rate and organization degree of the atrial activity bombarding the node is necessary in order to understand the genesis of ventricular response during atrial arrhythmias.

This paper introduces a new method to characterize AV conduction during spontaneous arrhythmic conditions, based on a bivariate analysis of atrial (node input) and ventricular (node output) time series. Specifically, the method is related to the construction of the AV synchrogram, which automatically identifies and quantifies transient instances of atrioventricular synchronization by performing a stroboscopic observation of the ventricular phase at times triggered by atrial activation. The approach adapts tools developed in the study of synchronization of coupled oscillators [20], [21], [22] to the atrioventricular setting, assuming that the heart can be modeled in terms of a system of coupled nonlinear oscillators [23], [24]. The performance of the AV synchrogram is evaluated on a dataset of atrial electrograms and ECG signals recorded during arrhythmic conditions, covering a wide range of atrial rates and organization levels, showing the ability of the technique to detect and quantitatively characterize AV conduction dynamics.

Section snippets

Data acquisition and dataset construction

The analysis was applied on a previously collected database of atrial electrograms (AEG) and surface ECG signals, recorded during electrophysiological studies in patients with spontaneous or pacing-induced episodes of atrial flutter and atrial fibrillation. During the study bipolar atrial electrograms were recorded by a catheter inserted into the esophagus in atrial flutter patients, and by a catheter positioned on the right atrial endocardial surface in atrial fibrillation patients.

AV synchrograms in different classes of atrial arrhythmias

Representative examples of AV synchrogram construction in the three types of arrhythmias are reported in Fig. 3, Fig. 4, Fig. 5. The synchrogram phases Ψm (m  3) are displayed in panels C–E, while the m/n ratios corresponding to the detected coupled sequences are summarized in panel F. Original atrial and ventricular interval series are reported in panels A and B as reference. Fig. 3 shows an example of AV coupling during typical atrial flutter. The atrium presented a regular activition at a

Discussion

This study introduces the AV synchrogram, a novel technique to provide a quantitative characterization of AV coupling during atrial arrhythmias. By combining the information of atrial and ventricular activation series, the synchrogram allows the identification of transient instances of AV synchronization of different n:m orders, which are automatically detected and characterized. The application of the technique to different classes of atrial arrhythmias shows the capability of synchrogram

Conclusions

Synchrogram analysis reveals changes in AV conduction and coupling stability following variations of atrial rate and complexity, and provides evidence for the role of atrial input in the generation of ventricular response during atrial arrhythmias. The AV synchrogram tracks the time course of AV coupling and reconstructs the dynamics of AV response in AF, showing the scaling effect of nodal recovery on atrial beats. This study demonstrates the feasibility of AV node characterization in the

Acknowledgements

Michela Masè is recipient of a fellowship supported by Fondazione Cassa di Risparmio di Trento e Rovereto. Leon Glass thanks the Natural Sciences and Engineering Research Council (Canada) for support.

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