Typical atrioventricular nodal re-entrant tachycardia: still many obscure points

This editorial refers to ‘Electrophysiology of anterograde right-atrial and left-atrial inputs to the atrioventricular node in patients with atrioventricular nodal re-entrant tachycardia’ by M. Šinkovec et al., on page 869. Our knowledge of the re-entry circuit of typical atrioventricular nodal re-entrant tachycardia (AVNRT) is limited, mainly on account of the unfeasibility of recording AV nodal potentials during an electrophysiological study and the lack of adequate animal models, as for other tachyarrhythmias. Early studies suggested that typical AVNRT was due to re-entry totally confined within the compact AV node as a result of functional dissociation between a fast pathway (FP) and a slow pathway (SP). This hypothesis was based on the observation that dual AV nodal physiology (jump ≥ 50 ms of A2H2 interval) was usually present in patients with AVNRT and appeared to be infrequent in control subjects. This jump was interpreted as representing induction block in the anterograde FP with selective conduction through SP. More recent studies suggested that SP and FP involved in the re-entry circuit of typical AVNRT represented conduction through different atrionodal connections, the site of earliest atrial activation being different between retrograde conduction over FP and SP. In other words, these pathways represent atrionodal connections outside the compact AV node rather than longitudinal dissociation within the AV node. There is extensive experimental and clinical electrophysiological evidence that the anterograde SP has its anatomic substrate in the inferior extensions of the AV node, located in Koch's triangle, which appear to constitute a necessary limb of the tachycardia circuit.1 There are two inferior extensions, one rightward and the other leftward, which are a direct continuation of the compact AV node; the rightward extension is much longer than the leftward one.1 In the vast majority of patients, the rightward extension appears to be involved in the re-entry circuit of typical AVNRT.1 The tachycardia circuit may occasionally involve the leftward extension, in which case a left-sided ablation procedure is needed.2 During programmed atrial stimulation, multiple discontinuities in the AV node conduction curve (multiple jumps) can be observed in 5–40% of patients with typical AVNRT.3 This electrophysiological finding probably reflects the presence of multiple anterograde SPs, as demonstrated in animal studies.2 However, in the majority of these patients, only one of the SPs appears to be involved in sustained tachycardia, though the involvement of up to three has been described.2 The retrograde FP is even less understood than the anterograde SP. In almost all patients with typical AVNRT, the earliest retrograde atrial activation occurs anteriorly, in the apex of Koch's triangle, and is recorded in the His bundle electrogram. The anatomical substrate of the retrograde FP has not been defined. Superior atrial inputs exist, but histological analysis of a small number of explanted human hearts with documented dual pathway physiology did not show any difference from normal hearts; in particular, a definite atrio-His bundle was not found.2 Superior atrionodal inputs consist of atrial myocardial cells that descend into the AV node and connect via a rim of transitional cells.1 However, long experience in the electrophysiology laboratory suggests that the retrograde FP has ‘Kent bundle-like’ properties, at least in the vast majority of patients with typical AVNRT. Indeed, the HA (or VA) interval does not display (or displays only minimally) decremental conduction; it remains constant during atrial stimulation even if marked variations in A2H2 duration are observed, during variations in AVNRT heart rate and during ventricular incremental pacing. Moreover, the HA interval does not change after administration of propranolol and atropine.4 These data suggest that, in many patients, the anatomic substrate of the retrograde FP is constituted by muscle fibres with fast conduction and not by the nodal and transitional cells, which should show decremental conduction. Anselme et al.5 performed simultaneous multisite catheter mapping of Koch's triangle during AVNRT and ventricular pacing at a similar cycle length. They found that during typical AVNRT, the earliest retrograde atrial activation was recorded near the apex of Koch's triangle in ∼90% of patients, confirming previous results. However, they have shown that the retrograde FP is heterogeneous within the area of Koch's triangle, both during tachycardia and during ventricular pacing. Multiple sites of early breakthrough in Koch's triangle, as well as a broad wavefront of activation (which were inconsistent with sequential activation from the apex of the triangle), were present in two-thirds of patients; moreover, in some patients, the earliest site of the retrograde activation sequence was in the coronary sinus or at the base of Koch's triangle. Furthermore, since a discordance in the retrograde activation sequence was present between ventricular pacing and AVNRT in about half the patients, the authors suggested that the retrograde FP was not an anatomically discrete structure, but dynamic for each patient. It could be hypothesized that the anatomic substrate of the retrograde FP is a network of muscle fibres; however, this interpretation is speculative and the mechanism of retrograde conduction remains obscure. A debated issue is whether the atrium is a necessary link in the re-entry circuit. The distance between the atrial connections of SP (posteriorly located) and the retrograde FP (anteriorly located) suggests that the re-entry circuit of typical AVNRT contains a relatively large component in which the impulse propagates from the atrial end of FP to the atrial end of SP. Long experience in the electrophysiology laboratory seems to confirm that the atrium is an integral component of the re-entry circuit. Indeed, in almost all patients, tachycardia does not start in the absence of a typical atrial echo beat, and stops when VA block occurs. However, in several case studies, the HH (and VV) intervals remained constant during typical AVNRT, although loss of the 1:1 tachycardia to atrium relationship—including the intermittent absence of P wave, retrograde Wenckebach or 2:1 block—was present. In rare cases, typical AVNRT has been seen to persist with constant ventricular rates while atrial fibrillation developed.6 In these cases, at least two mechanisms could be hypothesized. A different re-entry circuit may be involved; in this case, a common upper pathway consisting of transitional cells would link the anterograde and retrograde limbs, meaning that the atrium is not a necessary component of the circuit. The other possibility, which appears more plausible, is that a re-entry circuit is contained within a protected region of the atrium, which is, therefore, an integral component of the circuit. Catheter ablation of typical AVNRT, targeting SP at the base of Koch's triangle, is successful in >90% of patients. The most commonly accepted endpoint for the cure of AVNRT is the absence of inducibility of tachycardia before and during isoproterenol infusion. We reach this endpoint, but we do not really know how. In fact, after ablation, anterograde slow conduction, expressed by dual AV nodal physiology, persists during atrial stimulation in 31–69% of patients with typical AVNRT, and retrograde fast conduction persists in nearly all patients.7 In about half the patients, a typical single atrial echo beat occurs.7 Persistent AV nodal duality is more frequent in older patients8; the reason for this is unknown. In some patients, new onset of AV nodal duality appears after ablation.7 We do not know whether radiofrequency energy modifies the electrophysiological characteristics of SP or whether another ‘non-arrhythmic SP’ is involved. These data show that successful ablation of typical AVNRT is independent of specific modifications of anterograde AV conduction; we have previously speculated that this probably depends on critical nodal and perinodal tissue damage at different sites on the re-entry circuit.7,8 In other words, we deliver radiofrequency energy without knowing what we are really modifying. In medicine, there has always been a gap between pathophysiological knowledge and therapeutic possibilities; paradoxically, in the case of AVNRT, we cure almost all patients without really knowing what we are doing. Šinkovec et al.,9 by stimulating from the right atrial appendage and from the posterolateral coronary sinus, have provided further confirmation that the rightward posterior extension of the AV node is much more involved in the re-entry circuit of typical AVNRT than the leftward one. Moreover, the authors investigated the AV nodal electrophysiological characteristics after pharmacological autonomic blockade, and demonstrated a dominant role of the vagal system on resting SP conduction velocity. Indeed, after autonomic blockade, anterograde slow conduction was faster, as shown by significantly shorter maximum A2H2 intervals, and AVNRT was less inducible during programmed atrial stimulation. This finding is interesting because it may explain why, in many patients, spontaneous AVNRT occurs during the night or at rest, when the vagal tone is higher. However, in the literature there are contrasting results on the effects of the autonomic system on AVNRT. For example, in one study10 the cycle length of typical AVNRT significantly decreased after autonomic blockade, while in another it increased.4 These contrasting results may be explained by the different intensity of sedation and by environmental factors inside the electrophysiology laboratory, which could condition the resting sympathetic tone. The sympathetic system, too, seems to play a role in the onset of spontaneous AVNRT; indeed, in some patients, it starts mainly during exercise. During the electrophysiological study, isoproterenol infusion facilitates the onset of AVNRT, mainly in those subjects without spontaneous VA conduction.2 Our knowledge of the effects of the autonomic system on AVNRT is also limited, and, at present, it is not possible to formulate general rules. However, it seems that an increase in both vagal and sympathetic tone may facilitate the onset of tachycardia, as in the case of atrial fibrillation. Conflict of interest: none declared.