What Is Re-entry?

In its simplest form, re-entry is the circulation of the cardiac impulse around an obstacle; this leads to repetitive excitation of the heart at a frequency that depends on the conduction velocity of the circulating impulse and the perimeter of the obstacle (Figure 4-1).² According to the original description by George Mines, which was published in The Journal of Physiology in 1913, re-entry occurs around a fixed anatomic obstacle, and the physical disruption of the surrounding circuit will interrupt the activity. As illustrated in Figure 4-1, the initiation of the re-entrant activity depends on the occurrence of a unidirectional block in which activation takes place in only one direction within the circuit.

Figure 4-1 Circus movement re-entry around a ring of heterogeneous tissue surrounding an anatomic obstacle. re-entry is initiated by the application of a premature stimulus (red dot) to the upper branch. As the impulse enters the ring, it encounters tissue recovered on the left side. However, the tissue on the right has not yet recovered from previous excitation (not shown), and unidirectional block occurs. As a result, the wavefront begins to rotate around the obstacle. If the pathlength is long enough or the conduction velocity is slow enough, sufficient time is available for recovery on the upper right side of the ring, and sustained re-entry will be initiated. Note that in this hypothetical example, wavelength (WL), which is equal to the product of conduction velocity (CV) times refractory period (RP), is much shorter than the path length.

It is clear from Figure 4-1 that the rotation time around the circuit should be longer than the recovery period of all segments of the circuit. The extra time required for the impulse to successfully complete a rotation may result from a relatively large circuit, a relatively slow conduction velocity of the impulse, or the relatively short duration of the refractory period. Hence, the “wavelength,” which may be calculated roughly as the product of the refractory period and the conduction velocity, must be shorter than the perimeter of the circuit. An excitable region will separate the front of the impulse from its own refractory tail (i.e., excitable gap) and re-excitation will ensue.

Re-entry is responsible for various arrhythmias, including supraventricular and ventricular extrasystoles, atrial flutter, atrioventricular (AV) nodal reciprocating tachycardias, supraventricular tachycardias associated with accessory AV pathways, bundle branch ventricular tachycardias, and monomorphic ventricular tachycardias associated with myocardial infarction.

The classic model of anatomically determined re-entry depicted in Figure 4-1 is directly applicable to specific cases of tachyarrhythmias. These include supraventricular tachycardias occurring within the AV node or those using accessory pathways, as well as bundle branch re-entrant tachycardia. However, other types of re-entrant arrhythmias require somewhat different explanations for their mechanisms. For example, the cellular basis of closely coupled ventricular extrasystoles initiated somewhere in the Purkinje fiber network can be explained by the so-called reflection mechanism described by Antzelevitch et al in 1980 (Figure 4-2, A).³ Recently, reflection to and from an accessory pathway was shown to be a potential mechanism for the initiation of atrial fibrillation in patients with manifest (pre-excited) Wolff-Parkinson-White (WPW) syndrome.⁴

Figure 4-2 Two different forms of functional re-entry (i.e., in the absence of an anatomic obstacle). A, Reflection, where re-entry occurs over a single pathway in a linear bundle (e.g., a Purkinje fiber) across an area of depressed excitability (shaded). B, Functional re-entry in two-dimensional myocardium. Curved lines are isochrone lines showing consecutive positions of the wavefront. The curved arrow indicates the direction of rotation.

In the absence of a predetermined obstacle or circuit (Figure 4-2, B), however, many tachyarrhythmias that originate in the myocardium (atrial or ventricular) require mechanisms whereby re-entrant activation may occur as vortices of electrical excitation rotating around an area of myocardium. Accordingly, the impulse must circulate around a region of quiescence. In 1977, Allessie et al⁵ explained such functionally determined re-entry by proposing the so-called leading circle hypothesis, with its two variants of “anisotropic” re-entry described in 1988 by Dillon et al⁶ and “figure-of-8” re-entry proposed by El-Sherif⁷ in 1985. A somewhat different postulate for vortex-like re-entry, the “spiral wave re-entry” hypothesis, was put forth by Davidenko et al⁸ in 1992 and is derived from the theory of wave propagation in excitable media. Spiral wave re-entry attempts to provide a unifying explanation for the mechanisms of monomorphic and polymorphic ventricular tachycardias as well as the mechanism of fibrillation.

Circus Movement Re-entry

Undoubtedly, the concept of circus movement re-entry, in which a cardiac impulse travels around a predetermined circuit or around an anatomic obstacle, may be applied successfully to various clinical situations. Two clear examples of re-entrant arrhythmias based on the circus movement mechanisms are (1) supraventricular tachycardias observed in patients with WPW syndrome and (2) bundle branch re-entrant ventricular tachycardia, which is more commonly seen in patients with idiopathic dilated cardiomyopathy. All conditions required by the original idea of circus movement re-entry may be found in these two types arrhythmias, as follows:

Figure 4-3 A, Atrioventricular re-entry in the presence of an accessory pathway (AP). B, Bundle branch re-entry using the right bundle branch (RBB) and the left anterior fascicle (LAF) as the two major components of the circuit. AVN, Atrioventricular node; LBB, left bundle branch; LPF, left posterior fascicle.

Functionally Determined Re-entry

As Mines noted in 1913, circus movement re-entry results when an electrical impulse propagates around a one-dimensional circuit or ring-like structure. Although the model is entirely applicable to arrhythmias such as those observed in the presence of AV accessory pathways, it may not represent a realistic model for re-entrant arrhythmias occurring in the atria or ventricles. Re-entrant activity may, indeed, occur in the absence of a predetermined circuit—as shown later in 1973 and 1977 by Allessie, Bonke, and Schopman—where the electrical impulse may rotate around a region that is anatomically normal and uniform but functionally discontinuous.

In 1924, Garrey⁹ presented in an article in Physiological Reviews the first description of re-entrant excitation in the absence of anatomic obstacles in experimental studies on circus movement in the turtle heart. Garrey’s observations suggested that point stimulation of the atrium was sufficient to initiate a regular wave of rotation around the stimulus site. Subsequently, in 1946, Wiener and Rosenblueth¹⁰ developed the first mathematical model of circus movement re-entry, which supported waves of rotation around a sufficiently large barrier, but they could not demonstrate re-entry in the absence of an obstacle. This prompted Wiener and Rosenblueth to suggest that perhaps Garrey may have unwittingly produced a transient artificial obstacle near the stimulation site.

The “Leading Circle” Model

In 1973, Allessie, Bonke, and Schopman provided the first direct experimental demonstration that the presence of an anatomic obstacle is not essential for the initiation or maintenance of re-entry. These authors studied the mechanism of tachycardia in small pieces of isolated rabbit left atrium by applying single premature stimuli. Through multiple electrode mapping techniques, they demonstrated, in 1973 and 1977, that the tachycardias were based on rotating waves and suggested that such waves were initiated as a result of unidirectional block of the triggering premature input. Transmembrane potential recordings demonstrated that cells at the center of the vortex were not excited but developed local responses, which led to the development of the “leading-circle” concept of functional re-entry.

According to the leading-circle concept of Allessie and colleagues, in the absence of an anatomic obstacle, the dynamics of re-entry are determined by the smallest possible loop in which the impulse can continue to circulate. Under these conditions, the wavefront must propagate through relatively refractory tissue, in which case no “fully excitable gap” will be present and the wavelength will be very close to the length of the circuit. The leading circle idea paved the way for major advances in the understanding of functional re-entry. It served as a platform for developing a unifying hypothesis (spiral wave re-entry) that explains most of the major properties of functionally determined re-entry, which are commonly observed in normal cardiac muscle in experiments. This includes the phenomenon of re-entry “drift” described by Davidenko et al⁸ in 1992 and Pertsov et al¹¹ in 1993. Re-entry drift results in beat-to-beat changes in the location of the rotation center (see Drifting Vortices and Ventricular Fibrillation).

Anisotropic Re-entry

In 1986, Spach and Dolber¹² implicated microscopic structural complexities of the cardiac muscle in the mechanism of re-entrant activation in both atria and ventricles, particularly in relation to the orientation of myocardial fibers, the manner in which the fibers and fiber bundles are connected to each other, and the effective electrical resistivities that depend on fiber orientation. Because of these structural properties, propagation velocity in the cardiac muscle is three to five times faster in the longitudinal axis of the cells than along the transverse axis. Mapping studies performed by Peters and Wit¹³ in 1998, using multiple extracellular electrodes have shown that, in the setting of myocardial infarction, re-entry may occur in the survival epicardial rim of tissue. Under such conditions, the wave circulates around a functionally determined elongated region of block, the so-called line of conduction block (Figure 4-4, A). Based on the orientation of the line of block, it was thought that anisotropic propagation played a major role both in the initiation as well as in the maintenance of re-entry in ventricular tissue surviving a myocardial infarction (Figure 4-4, B). In addition, propagation velocity is exceedingly slow at the edges of the lines of block, which has also been attributed to anisotropic propagation.

Figure 4-4 Anisotropic re-entry around a line of block. Top panel, Curved lines are isochrones. The distance between lines denotes velocity of propagation. Velocity is faster in the horizontal direction than around the pivot points. Bottom panel, Example of re-entry around a line of block that was recorded in an isolated Langendorff-perfused murine heart with optical mapping. White lines are 1-ms isochrones. Time scale, 0 to 40 ms.

Figure-of-8 Re-entry

Figure-of-8 re-entry, described in 1987 by El-Sherif, Gough, and Restivo, has been recognized as an important pattern of re-entry in the late stages of myocardial infarction. In most cases, two counter-rotating waves coexist at a relatively short distance from each other (Figure 4-5). As described for the case of single re-entrant circuits, each wave of the figure-of-8 re-entry circulates around a thin line or arc of block. The region separating the lines of block is called the common pathway. A detailed description of the common pathway is of great practical importance, since there is evidence that it could be a strategic region for surgical or catheter ablation in this type of re-entry. In fact, unlike other forms of functionally determined re-entry, figure-of-8 re-entry may, indeed, be interrupted by physical disruption of the circuit. Several studies have attempted to describe the characteristics of propagation in the common pathway. However, the properties of the common pathway are still not clearly defined. It effectively behaves like an isthmus limited by two functionally determined barriers. In addition, there are two wavefronts that interact in the common pathway. As a result, propagation may be determined by a combination of factors other than those analyzed in most experimental studies such as anisotropy. The study of propagation across an isthmus and the influence of wavefront curvature may have significant implications in understanding the properties of the common pathway, as discussed in the next section.

Figure 4-5 Figure-of-8 re-entry. Left panel, Figure-of-8 re-entry consisting of two counter-rotating wavefronts, one in the clockwise direction and the other in the counterclockwise direction, around their respective lines of block. The wavefronts coalesce in the lower part of the circuits, and they move at varying velocities across the common pathway. Right panel, Activation map. Figure-of-8 re-entry recorded in optical mapping of an isolated Langendorff-perfused murine heart. White lines, 1-ms isochrones. Temporal scale, 0 to 17 ms.

Spiral Wave Re-entry