William J. Gibb

Adaptive classification of myocardial electrogram waveforms

The shape of myocardial electrogram complexes can change gradually in response to electrical and physiological transients. These changes could affect the reliability of morphologic-based electrogram classifiers proposed for use in implantable cardioverters. Here the authors present a method of detecting gradual changes in the shape of electrogram complexes and evaluate the method by incorporating it into a simple adaptive classification scheme. Of the six subjects recruited to take part in a previous comparative study of myocardial electrogram features, the authors observed extensive morphologic drift of normal sinus beats in two subjects. The results indicate that the adaptive classification scheme proposed here can reduce observed classification error rates compared to rates obtained without adaptation.<<ETX>>

Selection of myocardial electrogram features for use by implantable devices

Implantable devices that terminate ventricular tachycardia must be capable of correctly classifying heart rhythms to a high degree of reliability. The relative discriminating power of several myocardial electrogram features in six human subjects were evaluated by reducing the order of their corresponding feature spaces using three different optimization methods: minimizing univariate Bayes error rates (univariate parametric), maximizing the Kullback divergence (multivariate parametric), and pruning classification trees (nonparametric). It was found that although the composition of the optimal subspaces varied considerably from one subject to another, one frequency domain feature was common to most of the optimal subspaces.<<ETX>>

A computer model of dual AV nodal pathways: evidence for electrotonic interactions

In patients with atrioventricular (AV) nodal reentrant tachycardia, there exist two functional conducting pathways: a fast pathway with a larger effective refractory period, and a slow pathway with a shorter refractory period. Elimination of the slow pathway cures patients of their arrhythmia. It has been observed clinically that elimination of the slow pathway results in shortening of the effective refractory period of the fast pathway, the mechanism of which is not known. In a computer model of the AV nodes, the authors successfully tested the hypothesis that concealed conduction in the late-activating slow pathway exerts an electrotonic influence on the fast pathway, such that elimination of the slow pathway results in shortening of fast pathway action potential duration. The model consisted of resistively coupled elements exhibiting ionic current kinetics of calcium-driven action potentials.<<ETX>>

Modeling triggered cardiac activity: An analysis of the interactions between potassium blockade, rhythm pauses, and cellular coupling☆

It is known that under certain conditions, a combination of potassium channel blockade, sympathetic nervous activity, and pauses in sinus rhythm can increase the occurrence of cardiac arrhythmias. Although the arrhythmogenic interactions of these three factors are not completely understood, it is believed that the associated arrhythmias may be initiated by afterpotentials via a process that we refer to as propagated triggered activity. Using a two-cell computational model of ventricular action potential kinetics, we simulate nonuniform potassium blockade, sympathetic nervous activity, and pauses in sinus rhythm under conditions of hypokalemia. Under these conditions, the two-cell model suggests that (1) the arrhythmogenic interactions of potassium blockade and sympathetic nervous activity are highly dependent on heart rate; (2) triggered activity induced by potassium blockade would most likely occur during a pause in sinus rhythm; (3) during a sufficiently large pause in sinus rhythm, potassium blockade can induce triggered activity at normal levels of sympathetic activity; and (4) potassium blockade can increase the probability of triggered activity only if heart rate falls within a critical range. We also show that during pauses in sinus rhythm, two-cell triggering interactions between potassium blockade and sympathetic activity closely parallel the parametric displacement of the dynamic instability underlying the afterpotentials. Our results indicate that the behavior of the triggering mechanism studied here is consistent with that of pause-induced arrhythmias.

Geometric structures that facilitate triggered arrhythmias in ventricular myocardium

Abstrcrct--We simulated action potential propagation BcroBs a sheet of ventricular myocardium embedded with kinetic and structural heterogeneities. Under conditions of (1) differential kinetics of the secandary-inward and potassium currents, (2) uniform hypokalemia, and (3) heterogeneous transcellular resistivity, phase 2 early afterdepolarizations can trigger activity in neighboring tissue. In addition, we found three structural properties that facilitate triggered activity: (1) a combination of convex and concave segments along a barrier of relatively large resLPtivity separating heterogeneous myocardial structures, (2) an insulating barrier that encloses the heterogeneities except for a small conducting gap, and (3) a rudimentary wavegulde linking the conducting gap to the surrounding myocardium. With respect to triggered cardiac activity, these results highlight the importance of both kinetic and structural ventridar betemgeneitlea.

Reentry in non-uniformly anisotropie ventricular myocardium — Simulation and visualization in a computer model

We tested the hypothesis that non-uni-formly anisotropie coupling combined with variation in recovery properties provides the substrate for reentry by simulating a 22 × 8 mm sheet of myocardium as a grid of 17,600 elements obeying Beeler-Reuter kinetics. Barrier lines of relative transverse uncoupling defined a conducting isthmus. In separate experiments, we varied barrier resistivity, length and width. Membrane ionic properties were uniform throughout, except at the mouth of the isthmus where abnormal recovery properties were specified. We found that regional variation in cellular recovery properties allows for unidirectional block of premature extrastimuli and initiation of reentry, while-transverse uncoupling, when of the proper geometry, allows for perpetuation of tachycardia. Graphical visualization tools were developed to assist in interpreting the large amount of data produced by the computer model.

Polymorphic ventricular tachycardia in a model of triggered cardiac activity

It has been suggested that the cardiac arrhythmia known as torsades de pointes could be caused by competing foci of triggered activity. To examine this competitive triggering hypothesis, we used a model of ventricular action potential propagation to simulate two separate zones of heterogeneous myocardium under electrophysiologic conditions that have been correlated with the occurrence of torsades de pointes. We found that the two zones could trigger competitively, and that the corresponding electrogram morphology alternates as observed during episodes of torsades de pointes. These preliminary results are in accord with the competitive triggering hypothesis.

Early afterdepolarizations in a model of cardiac cells

Using a single Beeler-Reuter patch, we demonstrate that oscillatory responses of transmembrane potential can be simulated in the absence of a constant current stimulus by applying physiologically reasonable parametric variations to the model. Our results indicate that 1) the principal active elements of this periodicity could be limited to the Ca+2 kinetics, with the K+ kinetics playing a passive role, 2) these oscillations are capable of triggering sequences of entrained action potentials in a neighboring cell, and 3) partial K+ blockade can facilitate activation in the neighboring cell.

Reentry in a model of myocardium with fractal uncoupling

An attempt was made to test the hypothesis that in a model of the myocardium, the greater the degree of heterogeneous cell-to-cell uncoupling, the greater the likelihood of reentry. The authors modeled a sheet of myocardium with a 128*128 grid of resistively coupled cells exhibiting modified FitzHugh-Nagumo kinetics. The diffusion coefficients, inversely related to coupling resistivity, were assigned to produce a mottled, fractal pattern using a recursive algorithm operating across size scales. Each fractal tissue was then subjected to the same type of periodic pacing at small areas and from different locations. In a series of experiments, a direct relationship was found between the degree of heterogeneous uncoupling and the propensity for reentry. In addition, it was noted that there must be a critical amount of geometric clumpiness for reentry to occur. Reentrant waves were found to wander locally rather than circulate about a stationary point.<<ETX>>