The superior SP is a variant extending superiorly outside Koch’s triangle, which can be confirmed by electrophysiological observations of (1) the earliest site of retrograde atrial activation above the His bundle region, or (2) its successful selective ablation near the right side of the AV node or the non-coronary sinus of Valsalva, or (3) both [1]. We have described a distinct “superior-type” entity of fast-slow AVNRT using a superior SP as its retrograde limb [12]. However, before our report, several investigators had also hypothesized the existence of a substrate localized on top of the Koch’s triangle, responsible for atypical AVNRT. DiMarco et al. [13] reported a case of atypical AVNRT, with the earliest atrial site of activation located in the His bundle region and Wenckebach type AV block, and presumed that the reentry circuit was within the upper portion of the AV node, based on the responses of the tachycardia to atrial stimulation. This might have been the first published case of superior-type fast-slow AVNRT. Using intraoperative ice mapping Keim et al. [14] identified the first case of slow-fast AVNRT, where the SP extended superiorly into the interatrial septum. No case has since been reported of slow-fast AVNRT using a superior SP as the anterograde limb. In 3 cases of atypical fast-slow AVNRT, Nawata et al. [15] hypothesized the existence of a SP extending above the His bundle as a retrograde limb of the circuit. However, they did not proceed with ablation to confirm the presence of the SP. Cases reported by Otomo et al. [16] of atypical fast-slow AVNRT with a site of earliest atrial activation in the His bundle region, eliminated by ablation at the midseptal level, were probably similar to our “superior-type” of AVNRT. Lockwood et al. [17] also described, in the same period, the presence of an anterosuperior SP and associated atypical slow-slow or fast-slow AVNRT using this SP variant as the retrograde limb. No further case of superior SP has been reported, until our case where a superior SP was successfully ablated in the non-coronary cusp of the aortic valve [18].

We have, thus far, studied over 20 cases of superior-type fast-slow AVNRT (Fig. 1A). In this series, we have observed sites of earliest atrial activation and successful ablation in the superoanterior region of the right atrial free wall, along the tricuspid annulus, suggesting the presence of a “superoanterior” SP extending to the superoanterior right atrial wall [19, 20]. In some of these cases, retrograde conduction via the superoanterior SP was reproducible with ventricular stimulation [20] and occasionally revealed multiple atrial exits.

Fig. 1.

Distribution of the site of earliest atrial activation during fast-slow AVNRT using a superior, superoanterior or inferolateral right atrial SP (A) and schematic illustration of the reentry circuits of an atypical fast-slow AVNRT using variants of SP, the AV ring (AVR) and the retroaortic node (RAN) (B). NCS, non-coronary sinus of Valsalva, TA, tricuspid annulus. (B) The AVR encircling the TA is continuous with the right inferior extension (RIE) of the AV node and with the RAN, just behind to NCS. The inferolateral right atrial slow pathway (inf-lat-RA-SP) is formed by the continuous RIE and AVR, and is used as the retrograde limb of the reentrant inferolateral-type of fast-slow AVNRT. The superior slow pathway (sup-SP), formed by nodal-like tissue connecting the compact node (CN) and RAN, is used as the retrograde limb for the reentrant superior-type of fast-slow AVNRT. The superoanterior slow pathway (sup-ant-SP) is formed by the AVR in continuity with the RAN and the components of sup-SP, and is used as a retrograde limb of the reentry circuit of the superoanterior-type of fast-slow AVNRT.

Several histological studies support the presence of a superior or superoanterior SP. Inoue et al. [21] identified node-like tissue originating from the compact AV node and extending superiorly, named “superior extension”. Kato et al. [22] found an aggregation of node-like cells around the annulus in all hearts they studied. The genesis of the superior SP will be discussed later.

The superior-type of fast-slow AVNRT, the main subtype of AVNRT using a superior SP, is characterized by a long RP and a site of earliest atrial activation above the His bundle region during tachycardia [12]. Therefore, the electrophysiological diagnosis of this AVNRT is made by excluding (a) an atrial tachycardia originating in the vicinity of the AV node, and (b) AV reentrant tachycardia using a slowly conducting accessory pathway running in the perihisian region [12]. A diagnosis of AV reentrant tachycardia can be easily excluded by the observation of ventriculoatrial (VA) dissociation during ventricular overdrive pacing of the tachycardia [23, 24] or no change in the atrial cycle during the transition of QRS complexes immediately after ventricular overdrive pacing of the tachycardia [12, 25, 26]. The former, although not specific, is often observed during ventricular overdrive pacing of the superior-type, fast-slow AVNRT, probably because the retrograde conductivity of the lower common pathway decreases as the tachycardia develops, inhibiting the retrograde penetration into the AV nodal reentry circuit [12]. The latter may never occur with AV reentrant tachycardia using a right septal accessory pathway, due to the repetitive or fully premature retrograde penetration of the accessory pathway in the QRS transition zone during ventricular pacing from the site ipsilateral to the accessory pathway [27]. This is in contrast with AV reentrant tachycardia using a left lateral accessory pathway, where a false negative response is occasionally observed [27]. Moreover, the atrial preexcitation phenomenon typically diagnostic of AV reentry [28] and evidenced by atrial resetting of the tachycardia by a single premature ventricular stimulus delivered during His bundle refractoriness, may be absent if the tachycardia uses a slowly conducting accessory pathway, because of the decremental conduction caused by the ventricular stimulus [29]. Therefore, instead of single premature ventricular extrastimuli delivered during the tachycardia, we use ventricular overdrive pacing to differentiate atypical AVNRT from AV reentrant tachycardia and orthodromic reentrant tachycardia using concealed nodo-ventricular or nodo-fascicular fibers [30].

In contrast, the discrimination of sup-F/S-AVNRT versus atrial tachycardia remains challenging. Although the observations of (a) a V-A-V response upon ventricular induction/entrainment [31], and (b) termination of the tachycardia by ventricular pacing without atrial capture [32] are most useful to exclude the diagnosis of atrial tachycardia. The likelihood of these observations is low because of retrograde block occurring in the lower common pathway [12]. In fact, a V-A-V response upon ventricular entrainment is rare [16, 33]. Instead, one is more likely to observe several electrophysiological phenomena characteristic of this type of AVNRT. Understanding these phenomena facilitates a rapid and accurate diagnosis.

First, in AV nodal reentry, a strong link is believed to be present between ventricular and subsequent atrial activation during differential atrial entrainment pacing from multiple sites in the atria [34]. However, when pacing a superior-type of fast-slow AVNRT, VA linking may be occasionally absent, which can be recognized by a shorter VA interval after entrainment pacing from the high right atrium (HRA) than from the proximal CS [35]. This may cause an erroneous diagnosis of atrial tachycardia and is explained by a pacing site-dependent shortening of the retrograde conduction time over the SP, immediately after entrainment pacing. Indeed when the wavefront reaches earlier and penetrates deeper into the atrial end of the SP during entrainment pacing from site A than from site B, depending on the physical relationship between the site of pacing and dual AV nodal pathways, the subsequent retrograde conduction time over the SP is shorter after pacing from A than from B, due to decremental conduction [35].

Second, a dual atrial response resulting from simultaneous retrograde conduction over the fast and superior SP, causing a V-A-A-V response, is often observed, especially upon ventricular induction of a superior-type of fast-slow AVNRT [36]. Therefore, based on characteristics of the V-A-A-V response, a tachycardia with an earliest site of atrial activation in the His bundle region is an atrial tachycardia. We believe that the inter-electrograms analysis of the V-A-A-V response partially allows the discrimination between fast-slow AVNRT and atrial tachycardia: when the interatrial interval of the V-A-A-V response minus the tachycardia cycle length is defined as $\mathrm{\Delta }$AA, a $\mathrm{\Delta }$AA $>$26 ms is diagnostic of fast-slow AVNRT (the V-A-A-V response being due to a dual atrial response), whereas a $\mathrm{\Delta }$AA –80 ms is diagnostic of atrial tachycardia [30, 36].

Third, when the tachycardia is terminated by ventricular overdrive pacing, the atrial cycles immediately before the termination may lengthen transiently, due to repetitive retrograde conduction with a decremental delay over the superior SP, followed by orthodromic block inside the superior SP (Fig. 2). This is not simple ventricular entrainment nor termination without atrial capture, but a frequently observed, confirmatory, diagnostic phenomenon which excludes the diagnosis of atrial tachycardia.

Fig. 2.

Termination of fast-slow AVNRT using a superoanterior SP during ventricular overdrive pacing at an S-S cycle length of 425 ms from the right ventricular apex (RVA1-2). The site of earliest atrial activation during tachycardia is recorded in the HRA (HRA1-2). The atrial cycle length immediately after the 4th and 5th stimuli lengthens slightly without change in the atrial activation sequence, consistent with an orthodromic capture of the atria over the superoanterior SP, with a decremental delay in response to the 4th and 5th stimuli (dotted arrows). The 6th stimulus is blocked (straight arrow), evidenced by the absence of retrograde activation over the SP in its wake. In response to the 6th and 7th ventricular stimuli, the site of earliest retrograde atrial activation was observed in the distal electrogram of the His bundle region (HBE1-2) along with a short ventriculoatrial interval, consistent with retrograde conduction over a FP. The numbers above the HRA1-2 channel are the interatrial intervals. I, II and V${}_1$, surface electrocardiogram leads; CS 19-20 to 1-2, proximal to distal CS.

Fourth, ventricular extrastimulation after simultaneous stimulation of atrium and ventricle is useful to induce the superior-type of fast-slow AVNRT by exposing or accelerating a fragile retrograde conduction over the lower common pathway; however, this may cause a complex sequence of AV or VA activation, possibly leading to a misinterpretation of the AV or VA relationship. For example, when the tachycardia follows the last ventricular stimulus (Fig. 3A), it appears to be induced by that stimulus, creating a “pseudo-V-A-V response” (Fig. 3A), when in fact it was induced by atrial stimulation (Fig. 3A). Furthermore, when anterograde conduction of the 1st cycle of the induced tachycardia encounters the refractoriness produced by the last ventricular stimulus in the lower common pathway, the VA relationship upon induction reveals a V-A-A-V response (Fig. 3B) [37].

Fig. 3.

(A) pseudo-V-A-V and (B) atypical V-A-A-V responses observed upon initiation of the tachycardia after ventricular extrastimuli (S2) at S1-S2 coupling intervals of 280 (A) and 380 ms (B), following trains of simultaneous atrial and ventricular pacing at an S1-S1 cycle length of 400 ms, in a patient presenting with a superior-type of fast-slow AVNRT. Ventriculoatrial conduction was absent at baseline. In both (A) and (B), the interval between the last atrial S1 and the first atrial electrogram of the tachycardia is similar to the interval between the last atrial S and the first atrial electrogram of the tachycardia induced by regular atrial pacing at an S-S cycle length of 400 ms (C). Therefore, the tachycardia is presumed to be induced by the atrial pacing train and follow the ventricular S2, instead of being induced by the ventricular S2. This resulted in an apparent V-A-V, or pseudo-V-A-V (A), and atypical V-A-A-V responses due to anterograde block in the lower common pathway caused by its refractoriness in the wake of S2 (B). II, surface electrocardiogram lead II; HRA1-2, high right atrium; HBE1-2, His bundle electrogram; CS13-14 to 1-2, proximal to distal coronary sinus; RVA1-2, right ventricular apex.

Fifth, when the tachycardia is induced by atrial stimulation, AV block may occur only in the 1st cycle of the induced tachycardia due to anterograde block in the lower common pathway, thus representing an initial A-A-V activation sequence [19, 38]; however, this activation sequence is also observed upon the induction of atrial tachycardia and, therefore, is not specific.

Electro-anatomical activation mapping of tachycardia in the right atrium and, if possible, in the non-coronary sinus of Valsalva is mandatory to identify the precise location of the site of earliest atrial activation, which is presumed to be the atrial end of the superior SP. A particularly meticulous mapping should be performed along the tricuspid annulus to identify the presumed atrial end of a superoanterior SP. Albeit rare, the right-sided interatrial septum away from the tricuspid annulus may be the site of earliest atrial activation during tachycardia.

Since we first reported the superior-type, fast-slow AVNRT [12], several cases of this tachyarrhythmia have recently been reported by other Japanese [39, 40, 41] as well Chinese [42] investigators. In contrast, few reports of this AVNRT have hailed from western countries [43], probably because it is underdiagnosed as atrial tachycardia originating from the vicinity of the AV node, in absence of universal diagnostic criterion to discriminate it from atrial tachycardia. Further studies are needed to find new diagnostic criteria and resolve these issues.

Atypical, slow-slow AVNRT is another subtype of AVNRT using a superior SP in a retrograde direction [44, 45]. The electrophysiological manifestations of this subtype is (a) a long AH interval, (b) an earliest site of atrial activation above the His bundle, and (c) its successful elimination by ablation of a typical SP, mimicking the manifestations of typical slow-fast AVNRT [44, 45]. Its prevalence, though difficult to determine precisely, is probably 1% of all slow-slow AVNRT [45]. An apparent electrophysiological prerequisite for its development is fragile anterograde conduction properties of the FP, preventing a participation of the latter as the anterograde limb of AVN reentry, in contrast to its participation in the superior-type, fast-slow AVNRT. On the other hand, the observation during an electrophysiologic study of a slow-fast AVNRT using a superior SP as the anterograde limb has never been reported, besides a single case successfully treated during intraoperative cryomapping [14]. Simple differential atrial entrainment pacing may be a valid means of screening this atypical slow-fast AVNRT [46]. When ablation of a typical SP fails to eliminate an apparent slow-fast AVNRT, cryomapping should be used, in search of a variant of SP as the anterograde limb, including a superior SP.

The superior-type fast-slow AVNRT is curable by ablation of the superior SP. In general, the site of earliest retrograde atrial activation over the superior SP during tachycardia or during ventricular stimulation must be targeted to ablate its atrial insertion. However, if the site of earliest atrial activation cannot be located either in the right perihisian region or in the non-coronary sinus of Valsalva, due to a close earliness of atrial activation, the latter can be targeted as the first site of ablation attempt to avoid injury to the AV node. The delivery of radiofrequency energy to the non-coronary sinus of Valsalva should be limited to the site of recording of an atrial electrogram of the highest amplitude as possible (Fig. 4A, Ref. [19, 47]), since, in these cases, the atrial end of the superior SP is probably inserted into the interatrial septum. Successful applications of radiofrequency energy terminate the tachycardia by retrograde block in the superior SP, usually without development of an accelerated junctional rhythm. If several applications remain unsuccessful at that site, the target of ablation may be moved to the right perihisian region. To keep the site of ablation away from the compact node and minimize the risk of AV nodal injury, the target should be limited to immediately behind the membranous septum, above the level of His bundle activation, where the near-field atrial and far-field ventricular electrograms are present and no His bundle electrogram is visible (Fig. 4B).

Fig. 4.

Representative examples. (A,B) Superior-type of fast-slow AVNRT successfully ablated in the non-coronary sinus of Valsalva (A) and the right perihisian region (B). (C) Superoanterior type fast-slow AVNRT. (D) Inferolateral type fast-slow AVNRT: E: ATP-sensitive atrial tachycardia originating from the inferolateral right atrial wall, along the tricuspid annulus. Left panels (A) to (E): intracardiac electrograms during tachycardia at the site of successful ablation. The asterisks in C, D and E mark the prepotentials preceding the local atrial electrograms. II, surface electrocardiogram lead II; HBE1-2, His bundle electrogram; ABL1-2, distal pole of ablation catheter. Middle panels: right (B) and left (A,C,D,E) anterior oblique fluoroscopic views of the catheter positions at the site of successful ablation. The white arrow points to the tip of the ablation catheter. Right panels: left anterior oblique views of three-dimensional activation maps of the right atrium during tachycardia, using CARTO${}^{\text{TM}}$ (A to D) and Rhythmia${}^{\text{TM}}$ (E) systems. The yellow tags indicate the sites of recording of the His bundle electrogram. The middle panel of Fig. 4B is reproduced from Kaneko et al. [19] (Copyright © 2016, the American Heart Association), and the left, middle and right panels of Fig. 4D are reproduced from Kaneko et al. [47] (Copyright © 2019, the Japanese Circulation Society), with permission from the publishers.

Ablation of the superoanterior SP should begin at the site of earliest atrial activation, corresponding to its atrial end (Fig. 4C), as its precise trajectory, especially between its atrial end and the compact AV node, remains unidentified. Each radiofrequency application often causes a shift in the site of earliest atrial activation; therefore, multiple applications may be needed to treat each new site of earliest activation. This phenomenon suggests that the SP widens at its atrial end. More interestingly, low-frequency potentials preceding the local atrial activation are often detectable near the site of earliest atrial activation (Fig. 4C), probably reflecting retrograde activation of the superoanterior SP. These electrophysiological observations contrast with the superior SP, the retrograde activation of which is not always detectable. Intracardiac echocardiography may be useful to navigate the tip of the ablation catheter in the non-coronary sinus of Valsalva [48, 49, 47], the perihisian region [50] or along the tricuspid annulus [51, 52].

Since Sung et al. [4] recorded at the CS ostium the site of earliest atrial activation during retrograde conduction across a typical SP, its atrial end has been believed to be located near that ostium. Moreover, even accounting for interindividual variations in the length of the typical SP functioning as the actual pathway [53, 54], or in the location of the compact node itself [55], the typical SP is generally believed to be located within Koch’s triangle [56, 57]. However, this is not based on a precise identification of the atrial end of the typical SP at the site of earliest atrial activation during retrograde conduction.

When performing activation mapping of the right atrium during fast-slow AVNRT, we observed seven cases where the site of earliest atrial activation was in the inferior or inferolateral right atrial free wall, along the tricuspid annulus (Figs. 1,4D) [58]. Convinced of our diagnosis of fast-slow AVNRT, we named “inferolateral right atrial SP” this variant of SP with a breakthrough in the inferolateral right atrium. No other similar case has been reported except a single case report from a Japanese institution [59], probably because three-dimensional electroanatomical activation mapping to identify the site of earliest atrial activation during fast-slow AVNRT has been used by only a few electrophysiologists [60]. Recent anatomical studies have described a right inferior extension of the AV node into the cavo-tricuspid isthmus [56]. The genesis of the inferolateral right atrial SP will be discussed later.

During tachycardia, slightly wider and sometimes biphasic (+/-) P waves in the inferior leads (Figs. 4D,5) [58] is a unique electrocardiographic/intracardiac characteristic of fast-slow AVNRT using an inferolateral right atrial SP as the retrograde limb (inferolateral fast-slow AVNRT), compared to typical fast-slow AVNRT. The atrial activation sequence during inferolateral, fast-slow AVNRT is unique: the site of earliest atrial activation is consistently recorded in the proximal CS; however, the atrial electrogram in the HRA relative to the His bundle region is recorded earlier than during typical, fast-slow AVNRT, due to a lateral atrial breakthrough away from the posterior septum (Figs. 4D,5).

Fig. 5.

Differential atrial entrainment pacing at an S-S cycle length of 365 ms from the high right atrium (HRA1-2) (A) and the proximal coronary sinus (CS9-10) (B), in a patient presenting with fast-slow AVNRT using an inferolateral, right atrial SP. This patient is the same as in Fig. 4D. Note: (1) the atypical atrial activation sequence during tachycardia, characterized by nearly simultaneous atrial electrograms in the HRA and in the His bundle region (HBE1-2); and (2) shorter His-atrial intervals immediately after entrainment pacing (indicated by horizontal bidirectional arrows and numbers above) in the HRA than in the proximal coronary sinus (CS9-10). II, surface electrocardiogram lead II; CS13-14 to 1-2, proximal to distal coronary sinus; RVA, right ventricular apex.

In our experience, inferolateral fast-slow AVNRT is easily diagnosed, using standard criteria [58]. First, a V-A-V response upon ventricular induction/entrainment is often observed [31], probably because retrograde conduction in the lower common pathway is preserved, excluding the diagnosis of atrial tachycardia. Second, a diagnosis of AV reentrant tachycardia using a slowly conducting, posterolateral or posterior accessory pathway as the retrograde limb can be easily excluded by the absence of change in the atrial cycles during the transition zone of the QRS complex, immediately after ventricular entrainment [25, 26]. As mentioned earlier, in a diagnosis of superior type fast-slow AVNRT, we favor ventricular overdrive pacing during tachycardia instead of single ventricular extrastimuli to exclude AV reentrant tachycardia and orthodromic reentrant tachycardia using concealed nodo-ventricular or nodo-fascicular fibers. Single extrastimuli or overdrive pacing from the right ventricular base contralateral to the site of earliest atrial activation may also help in the exclusion of these accessory pathway-mediated tachycardias [29, 61]. Differential ventricular entrainment pacing from the right ventricular apex and base may also be useful to exclude AV reentrant tachycardia [62].

We present a unique response to differential atrial entrainment pacing of inferolateral fast-slow AVNRT. Differential atrial entrainment pacing of typical fast-slow AVNRT may reveal the absence of VA linking, characterized by a shorter VA interval after pacing from the proximal CS than from the HRA, due to the pacing site-dependent effect described earlier [35]. In contrast, differential atrial entrainment pacing of inferolateral, fast-slow AVNRT may reproducibly reveal a reverse relationship of the VA interval, characterized by a shorter VA interval after pacing from the HRA than from the proximal CS (Fig. 5). This may be due to the atypical location of the atrial end of the SP, relatively away from the proximal CS and closer to the HRA, causing a deeper penetration into the SP during pacing from the HRA than from the proximal CS. The subsequent retrograde conduction time over the SP is, therefore, shorter after pacing from the HRA than from the proximal CS. This information may be helpful when interpreting the results from differential atrial entrainment pacing of fast-slow AVNRT.

An inferolateral right atrial SP can be successfully ablated, using the standard techniques applied for typical SP, or at the site of earliest atrial activation [58]. An accelerated junctional rhythm developing during ablation may be due to heating of the AV nodal transitional cells constituting these SP [58, 63]. However, in some patients, the tachycardia may be refractory, requiring the delivery of multiple radiofrequency applications due to shifts of the site of earliest atrial activation during tachycardia after each application [58, 59], similar to the observations made during ablation of superoanterior SP described earlier. This may also indicate the presence of a relatively wide SP with multiple connections into the atrial muscle [58]. Based on these observations, we recommend using the standard technique targeting the posteroseptum to eliminate a right, inferolateral atrial SP as first choice, irrespective of the site of earliest atrial activation, or as alternate choice when ablation at the site of earliest atrial activation is unsuccessful.

In most patients with inferolateral fast-slow AVNRT, low-frequency potentials preceding local atrial electrograms are detectable near the site of earliest atrial activation during tachycardia (Fig. 4D) [58]. These potentials may reflect retrograde activation over an inferolateral right atrial SP [58].