American College of Cardiology

Blomström-Lundqvist ET AL., MANAGEMENT OF PATIENTS WITH Supraventricular Arrhythmias
J Am Coll Cardiol 2003;42:1493–531

ACC/AHA/ESC Guidelines for the Management of Patients With Supraventricular Arrhythmias

A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Supraventricular Arrhythmias)

III. GENERAL MECHANISMS OF
SUPRAVENTRICULAR ARRHYTHMIA

A. Specialized Atrial Tissue

The sinoatrial (SA) node, atria, and AV node are heterogeneous structures (20). There is distinct electrophysiological specialization of tissues and cells within these structures. In the case of the nodes, cellular heterogeneity is a prominent feature. In the atria, cellular heterogeneity is not prominent, but there are marked complexities of tissue structure that have important implications for impulse propagation and the production of arrhythmias (21).

The SA node is a collection of morphologically and electrically distinct cells (22-28). The central portion of the sinus node, which houses the dominant pacemaking function, contains cells with longer action potentials and faster rates of phase 4 diastolic depolarization than other cardiac cells (28,29). The varied electrophysiological phenotypes of cells within the sinus node are due to a distinctive pattern of ion channel expression in the different cell types. Differences in the electrophysiological properties of cells within the node and differences in the expression and distribution of intercellular ion channels or connexins insulate SA nodal tissue from the electrotonic influences of the surrounding atrial myocardium (27,29,30).

Heterogeneity of the action potential profiles in the atria has been described (21,31,32). The underlying ionic current basis for the spatial differences in atrial action potentials has also been described in animal models. In the right atrium of the dog, cells from the crista terminalis exhibit the longest action potential durations when compared to cells isolated from the appendage and pectinate muscles, which have intermediate duration action potentials and myocytes from the AV ring, which exhibit the shortest action potential duration. Differential expression of calcium and transient outward and delayed rectifier potassium currents produce the differences in the action potential profiles and durations (33). Shorter action potential durations are observed in the left compared with the right atrial myocytes, the result of more robust expression of the rapid component of the delayed rectifier potassium current in the left atrium (34).

Cellular recordings support the existence of distinct populations of cells in the mammalian AV node (35). Ovoid cells have a nodal (N- or NH-type) action potential configuration (ie, action potentials with slow [Ca channel–dependent] phase 0 upstrokes and prominent phase 4 diastolic depolarization). In contrast, rod-shaped cells have action potentials more similar to action potentials recorded in atrial myocytes (AN-type) with rapid Na channel–dependent upstrokes and little phase 4 diastolic depolarization (35). Differences in ion channel expression underlie the differences in the electrophysiological behavior of each of the cell types. Variation in cell phenotype and intercellular connectivity cause differences in tissue-level conduction velocity, refractory period, and automaticity.

B. General Mechanisms

All cardiac tachyarrhythmias are produced by one or more mechanisms, including disorders of impulse initiation and abnormalities of impulse conduction. The former are often referred to as automatic; the latter as re-entrant. Tissues exhibiting abnormal automaticity that underlie SVT can reside in the atria, the AV junction, or vessels that communicate directly with the atria, such as the vena cava or pulmonary veins (36-38). The cells with enhanced automaticity exhibit enhanced diastolic phase 4 depolarization and, therefore, an increase in firing rate compared with pacemaker cells. If the firing rate of the ectopic focus exceeds that of the sinus node, then the sinus node can be overdriven and the ectopic focus will become the predominant pacemaker of the heart. The rapid firing rate may be incessant (ie, more than 50% of the day) or episodic.

Triggered activity is a tachycardia mechanism associated with disturbances of recovery or repolarization. Triggered rhythms are generated by interruptions in repolarization of a heart cell called afterdepolarizations (Fig. 1). An afterdepolarization of sufficient magnitude may reach “threshold” and trigger an early action potential during repolarization. Delayed afterdepolarizations (DADs) have been described in a variety of mammalian atrial tissues and cells exposed to mechanical stress (39), digitalis, or neurohormonal stress (40-47). It has been suggested that multifocal atrial tachycardia (MAT) is the result of DAD-induced triggered automaticity (48,49). Early afterdepolarizations have also been observed in human atrial myocardium (50) and pulmonary vein myocytes (51).

The most common arrhythmia mechanism is re-entry. Indeed, the first proven re-entry circuit in humans was that composed of the atrium, AV node, ventricle, and accessory pathway in patients with AV re-entry tachycardia. Re-entry may occur in different forms. In its simplest form, it occurs as repetitive excitation of a region of the heart and is a result of conduction of an electrical impulse around a fixed obstacle in a defined circuit. This is referred to as re-entrant tachycardia, and there are several requirements for its initiation and maintenance. Initiation of a re-entrant tachycardia requires unidirectional conduction block in one limb of a circuit. Unidirectional block may occur as a result of acceleration of the heart rate or block of a premature impulse that impinges on the refractory period of the pathway. Slow conduction is usually required for both initiation and maintenance of a re-entrant tachycardia. In the case of orthodromic AV re-entry (ie, anterograde conduction across the AV node with retrograde conduction over an accessory pathway), slowed conduction through the AV node allows for recovery of, and retrograde activation over, the accessory pathway. A requirement for the maintenance of such a tachycardia is that the wavelength of the tachycardia (ie, the product of the conduction velocity and the refractory period) must be shorter than the pathlength of the circuit over which the impulse travels. Too long a wavelength or too short a pathlength will result in the extinction of the tachycardia as the activation wavefront impinges on the inexcitable refractory tail terminating propagation. The amount by which the pathlength exceeds the wavelength represents the excitable gap. Antiarrhythmic drugs may interrupt re-entrant tachycardia by altering the relationship between the pathlength and the wavelength. Drugs with class III action prolong refractoriness and, therefore, the wavelength, thereby eliminating the excitable gap (52,53). Alternatively, drugs with class I action may interfere with conduction, often in the region of slow conduction-producing bidirectional block and inability to initiate or maintain the tachycardia.

Re-entry is the mechanism of tachycardia in SVTs such as AVRT, AVNRT and atrial flutter; however, a fixed obstacle and a predetermined circuit are not essential requirements for all forms of re-entry. In functionally determined re-entry, propagation occurs through relatively refractory tissue and there is an absence of a fully excitable gap (54). Specific mechanisms are considered in the following sections.