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Supraventricular Tachycardia

2018; Lippincott Williams & Wilkins; Volume: 11; Issue: 12 Linguagem: Romeno

10.1161/circep.118.006953

1941-3149

Bruce B. Lerman, Steven M. Markowitz, Jim W. Cheung, Christopher F. Liu, George Thomas, James E. Ip,

Atrial Fibrillation Management and Outcomes

HomeCirculation: Arrhythmia and ElectrophysiologyVol. 11, No. 12Supraventricular Tachycardia Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessReview ArticlePDF/EPUBSupraventricular TachycardiaMechanistic Insights Deduced From Adenosine Bruce B. Lerman, MD, Steven M. Markowitz, MD, Jim W. Cheung, MD, Christopher F. Liu, MD, George Thomas, MD and James E. Ip, MD Bruce B. LermanBruce B. Lerman Bruce B. Lerman, MD, Division of Cardiology, Department of Medicine, Cornell University Medical Center, 525 E 68th St, Starr 4, New York, NY 10021. Email E-mail Address: [email protected] Division of Cardiology, Department of Medicine, Cornell University Medical Center, New York, NY. , Steven M. MarkowitzSteven M. Markowitz Division of Cardiology, Department of Medicine, Cornell University Medical Center, New York, NY. , Jim W. CheungJim W. Cheung Division of Cardiology, Department of Medicine, Cornell University Medical Center, New York, NY. , Christopher F. LiuChristopher F. Liu Division of Cardiology, Department of Medicine, Cornell University Medical Center, New York, NY. , George ThomasGeorge Thomas Division of Cardiology, Department of Medicine, Cornell University Medical Center, New York, NY. and James E. IpJames E. Ip Division of Cardiology, Department of Medicine, Cornell University Medical Center, New York, NY. Originally published13 Dec 2018https://doi.org/10.1161/CIRCEP.118.006953Circulation: Arrhythmia and Electrophysiology. 2018;11:e006953Although the cardiac electrophysiological effects of adenosine were first recognized 90 years ago, it took an additional 60 years for it to emerge as a highly effectively clinical agent for the acute termination of supraventricular arrhythmias involving the atrioventricular node.1–3 Because electrophysiologists are well familiar with this use of adenosine, our attention will instead focus on the unique properties of the nucleoside that make it a specific electrophysiological probe for identifying underlying supraventricular arrhythmogenic mechanisms and confirming ablative success. For those interested in adenosine's contrasting effects in ventricular arrhythmias, one may refer to a recent review.4Adenosine is a potent but underutilized tool that is useful for clarifying the clinical diagnosis of seemingly obscure or poorly understood arrhythmias. Adenosine provides insights that are independent of and synergistic with those obtained with standard pacing maneuvers routinely used to uncover supraventricular mechanisms, such as entrainment, resetting, or para-Hisian pacing. The advantages of adenosine are that its effects are short-lived (on the order of several seconds), its effects are potent, and its signal transduction cascade mediates a multiplicity of electrophysiological effects that no other single agent replicates, each of which offers unique insights into electrophysiological phenomena and mechanisms.Electrophysiological Effects: Sinoatrial Node, Atrium, and Atrioventricular NodeAdenosine mediates its electrophysiological effects through binding to the cell surface A1R (adenosine receptor), a GPCR (G-protein–coupled receptor). In supraventricular tissue, activation of Gi/o results in release of Gβγ subunits, which activate the G-protein–coupled inward rectifying K+ channel and the time-independent current IKAdo.5 Common to both supraventricular and ventricular tissue, adenosine also inhibits cAMP-stimulated increases of the L-type calcium current, ICaL, through activation of Gαi2/Gαo.6Sinoatrial NodeIn the sinoatrial node, activation of IKAdo by adenosine results in negative chronotropy (a manifestation of its moderate effects on membrane hyperpolarization) and a decrease in rate of phase 4 depolarization (Figure 1).7,8 Incremental doses of adenosine result in further hyperpolarization of sinoatrial node membrane potential, causing sinus arrest.8 Under conditions of β-adrenergic receptor–cAMP stimulation, adenosine attenuates augmented levels of ICaL and If, an inward current activated by hyperpolarization. These effects are referred to as indirect because adenosine does not affect these currents in the absence of cAMP stimulation.8 Therefore, the net effect of adenosine on the sinoatrial node is to slow the rate, under both basal conditions (via activation of IKAdo) and β-adrenergic–stimulated conditions (inhibition of ICaL and If).Download figureDownload PowerPointFigure 1. Electrophysiological effects of adenosine on the sinus node.A, Spontaneous sinoatrial (SA) nodal rhythm from a rabbit heart with a maximum diastolic potential (MDP) of −62 mV. B, Slowing of SA node with adenosine (10 µmol/L). C, A larger dose of adenosine causes hyperpolarization and sinus arrest. D, Washout of adenosine. Reprinted from Belardinelli et al8 with permission. Copyright © 1988, the Physiological Society.AtriumAdenosine also mediates its cellular effects in atrial and atrioventricular nodal cells primarily through activation of IKAdo. In atrial myocytes, this results in shortening of action potential duration and a decrease in refractoriness.9 However, unlike the response in sinoatrial nodal cells, resting membrane potential is unaltered (Figure 2). By shortening the atrial refractory period without changing atrial conduction velocity, the wavelength of activation is shortened—a mechanism through which adenosine can facilitate induction of atrial fibrillation. Adenosine also exerts an antiadrenergic effect in atrial tissue, reducing cAMP-stimulated levels of ICaL.10 Similarly, other downstream effects of cAMP protein and kinase A activation are also attenuated by adenosine, including phosphorylation of the ryanodine receptor and activation of the sodium-calcium exchanger (INCX) and transient inward current ITI. The clinical implications of these effects will be discussed in further detail when specific atrial tachyarrhythmias are addressed below. Although ICaL is thought to have no role in abbreviation of atrial action potential duration—an effect completely attributable to IKAdo, some data suggest that adenosine may have a small effect, up to a 12% decrease in unstimulated ICaL,11,12 whereas other studies suggest its effects on ICaL are entirely indirect (antiadrenergic).13 Adenosine has no known effect on ICaT.11Download figureDownload PowerPointFigure 2. Electrophysiological effects of adenosine (ADO) on atrial tissue. ADO shortens atrial action potential duration without changing resting membrane potential (left). Right, ADO-induced current-voltage relationship from a guinea pig atrial myocyte. ADO-induced outward current (IKAdo) shows inward rectification and a reversal potential at approximately the potassium equilibrium potential (EK) of −90 mV. Reprinted from Belardinelli et al9 with permission. Copyright © 1983, the American Physiological Society.Atrioventricular NodeAdenosine has a negative dromotropic effect on the atrioventricular node and has differential effects on its constituent cells: atrionodal, nodal, and nodal-His bundle cells. The most potent effects of adenosine are expressed in nodal cells. In these cells and in atrionodal cells, adenosine decreases excitability by reducing the plateau amplitude and abbreviating action potential duration.14 In addition, it reduces the rate of rise of the upstroke in nodal cells. Nodal-His bundle cells are insensitive to adenosine. A summary of the effects of adenosine on the action potential in atrial tissue and atrioventricular nodal cell types is illustrated in Figure 3. Adenosine-induced atrioventricular node and ventriculoatrial block occurs at the level of the nodal cells due to complete abolition of nodal-cell action potentials. Although not definitively confirmed, adenosine's depressant effects on action potential amplitude in atrionodal and nodal cells may also in small part be due to slight reductions in basal ICaL and If. Of note, however, adenosine's effects on ICaL occur at concentrations greater than those that activate IKAdo.10Download figureDownload PowerPointFigure 3. Electrophysiological effects of adenosine on the atrioventricular (AV) node.Top, Representative action potential responses to adenosine in 3 cell types of the AV node. Adenosine decreases action potential duration in atrionodal (AN) cells, decreases maximum upstroke velocity, action potential amplitude, and duration in nodal (N) cells, and has no effect in nodo-Hisian (NH) cells. Bottom compares the relative electrophysiological effects of adenosine on an N cell and an atrial myocyte over time. In the atrial cell, adenosine primarily shortens action potential duration, whereas in the N cell, adenosine causes a delay in activation and a progressive decrease in action potential amplitude, resulting in depression of the action potential and eventually inexcitability by completely abolishing the action potential (after 2 min of exposure to adenosine). Reprinted from Clemo et al14 with permission. Copyright © 1986, American Heart Association, Inc.The diverse properties of adenosine enumerated above have practical utility in characterizing tissue properties in unusual tachycardia circuits and in defining the mechanism of tachycardia. We will demonstrate these principles by examining the effects of adenosine under 4 clinical conditions: decremental atrial myocardium, unmasking tachycardia circuits, uncovering dormant conduction post-ablation, and distinguishing among mechanisms of focal atrial tachycardia (AT).Decremental ConductionRetrograde Decremental Accessory PathwaysConsistent with adenosine's cellular effects, it has no appreciable effect on atrial conduction in normal atrial tissue or accessory pathways (APs). However, under conditions where abnormal atrial propagation results in decremental conduction, atrial tissue becomes responsive to adenosine, resulting in conduction block.15 The most common scenario involves decremental APs. Retrograde decremental APs are usually associated with long RP′ tachycardia, including but not limited to the permanent form of junctional reciprocating tachycardia. Adenosine terminates this form of tachycardia in the retrograde AP limb.16 A lingering debate centers on whether the retrograde AP in these patients is an accessory atrioventricular node or a decremental AP. In support of the latter is histological confirmation that the retrograde pathway in the permanent form of junctional reciprocating tachycardia is composed of atrial fibromuscular bundles, not atrioventricular nodal tissue.17 Therefore, consistent with these findings, decremental APs most often behave like atrial tissue with partially depolarized membrane potentials and depressed fast Na+ channel activity, accounting for their atypical conduction properties and adenosine sensitivity.The mechanism by which adenosine causes conduction block in retrograde decremental APs is thought to be by hyperpolarizing the pathway's membrane potential. In normal atrial cells, as in nondecremental APs, adenosine has little effect on resting membrane potential because membrane potential is near EK. However, when atrial membrane potential is depressed to ≤−70 mV (similar to a presumed decremental AP), adenosine causes hyperpolarization, making the cells inexcitable.9 An example of adenosine termination of atrioventricular reciprocating tachycardia in a retrograde decremental AP during is shown in Figure 4A.Download figureDownload PowerPointFigure 4. Effects of adenosine on anterograde and retrograde decremental accessory pathways.A, Sensitivity of a retrograde decremental accessory pathway to adenosine during atrioventricular (AV) reciprocating tachycardia. Adenosine caused progressive slowing in the retrograde pathway before terminating tachycardia within the pathway. Surface leads I, aVF, and V1 are shown, as well as intracardiac recordings from the high right atrium (HRA), His bundle electrogram (HBE), and coronary sinus (CS). B, Decremental anterograde accessory pathway. During atrial pacing at 430 ms, the stimulus to delta-wave interval shows progressive prolongation. C, During atrial pacing, adenosine causes conduction block in the anterograde decremental accessory pathway (*). Block also occurred in the AV node several beats later (not shown). d indicates distal; m, mid; p, proximal; and RVa, right ventricular apex. Reprinted from Lerman et al16 with permission. Copyright © 1987, American Heart Association, Inc (A). Reprinted from Ip et al18 with permission. Copyright © 2013, American Heart Association, Inc (B and C).Anterograde Decremental APsAdenosine has been helpful in illuminating differences in etiology of decremental conduction in the 3 predominant forms of anterograde decremental APs: atrioventricular pathways, atriofascicular pathways, and nodoventricular pathways. Although conduction in all 3 types of pathways is abolished by adenosine, adenosine's effects differ with respect to the type of pathway. For instance, decremental atrioventricular APs, which insert into the ventricle at the level of the tricuspid annulus, and atriofascicular pathways have intrinsic decremental properties and as such are sensitive to the direct effects of adenosine (Figure 4).18,19 In contrast, nodoventricular pathways typically arise from the slow atrioventricular nodal pathway20–22 and owe their apparent conduction properties to decremental conduction originating from the slow atrioventricular nodal pathway. Therefore, abolition of conduction over nodoventricular pathways with adenosine is a passive response, one that is primarily dependent on adenosine's effects on slow atrioventricular nodal pathway conduction.22Unmasking Retrograde Concealed ConductionAdenosine-mediated unmasking of conduction is observed under 2 conditions: (1) in the context of silent retrograde AP conduction that is concealed secondary to relatively more rapid conduction over the atrioventricular node, or when there is fusion of conduction over the 2 pathways (ie, atrioventricular node and AP) or (2) in the presence of left-sided retrograde fast or slow atrioventricular nodal pathways that masquerade as a left-sided retrograde AP.Due to adenosine's transient negative dromotropic effects on atrioventricular nodal conduction, it is an ideal agent to initially assess for the presence of a concealed, nondecremental AP in patients with supraventricular tachycardia. The persistence of ventriculoatrial conduction during ventricular pacing in response to adenosine (≤24 mg) is 90% sensitive and specific for detecting a retrograde AP and inducible atrioventricular reciprocating tachycardia, irrespective of AP location. Furthermore, adenosine-induced ventriculoatrial block predicts noninducibility of atrioventricular reciprocating tachycardia (96% negative predictive value).23Nonetheless, there are challenges in assessing retrograde ventriculoatrial conduction. Pacing maneuvers, including para-Hisian pacing24 and apical versus basal right ventricular pacing,25 are designed to distinguish between conduction over septal APs and the atrioventricular node. These maneuvers are less useful when AP conduction is masked by more rapid conduction over the atrioventricular node, when there is retrograde fusion between the AP and atrioventricular node or when there is a left-sided AP. In these indeterminate cases, adenosine can unmask silent AP conduction. The differential effects of adenosine on the atrioventricular node and AP can disclose the unexpected presence of a nondecremental AP during adenosine-induced atrioventricular node block.Six percent of patients with supraventricular tachycardia have eccentric retrograde conduction because of either a left-sided retrograde fast or slow atrioventricular nodal pathway.23 Adenosine is useful in unmasking these atypically located atrioventricular nodal pathways (inputs), which participate in atrioventricular nodal reentrant tachycardia. Figure 5 shows an example of left-sided retrograde atrial activation during right ventricular pacing. Ventriculoatrial conduction is transiently abolished with adenosine, and entrainment of the tachycardia is associated with a V-A-V response and a corrected postpacing interval minus tachycardia cycle length of 136 ms, consistent with an atypical form of slow-fast atrioventricular node reentry, with the retrograde limb comprising a left-sided fast atrioventricular nodal pathway.Download figureDownload PowerPointFigure 5. Adenosine unmasking of left-sided retrograde fast atrioventricular (AV) nodal pathway.A, Right ventricular (RV) pacing discloses earliest retrograde atrial activation recorded in the posterior-posterolateral coronary sinus (CS) catheter (white circle in right panel). During pacing, adenosine (ADO) induced ventriculoatrial (VA) block (arrow in left). Since there was no decremental VA conduction during ventricular pacing (not shown), the presence of an ADO-sensitive accessory pathway was considered unlikely. Therefore, ADO-induced VA block suggested the presence of an eccentric retrograde fast pathway. B, The presumptive diagnosis was confirmed during induction of the clinical tachycardia. Entrainment demonstrated a difference between the postpacing interval (PPI) and tachycardia cycle length (TCL) of 136 ms, indicating that the left-sided fast AV nodal pathway comprised the retrograde limb of AV nodal reentrant tachycardia. HB indicates His bundle; HRA, high right atrium; RVA, right ventricular apex; and SVT, supraventricular tachycardia. Other abbreviations as previously described. Reprinted from Liu et al23 with permission. Copyright © 2017, American College of Cardiology Foundation.There are relative limitations in using adenosine to unmask retrograde conduction, including relative insensitivity of the retrograde fast atrioventricular nodal pathway to adenosine. This occurs in ≈9% of patients who receive ≤24 mg of adenosine. Similarly, because as many as 6% of patients with retrograde APs and supraventricular tachycardia have decremental, adenosine-sensitive pathways, adenosine-induced ventriculoatrial block is not always indicative of block in the atrioventricular node.23 Nevertheless, despite these exceptions, adenosine has the potential to provide unique insights into supraventricular tachycardia mechanisms and offers key complementary data to that acquired by standard pacing maneuvers alone.Dormant ConductionAdenosine can elicit dormant conduction, defined as the restoration of excitability by adenosine in tissue rendered inexcitable by partial cellular damage secondary to ablation. There are at least 3 discrete clinical scenarios in which adenosine reveals dormant conduction: after pulmonary vein isolation,26 after achieving bidirectional cavotricuspid isthmus block,27 and after successful ablation of anterograde and retrograde APs.28 For the purpose of this discussion, we will focus on AP ablation as a general model for this phenomenon.The basis for dormant conduction rests on evidence that ablation can cause reversible injury to atrial myocardium, depolarizing atrial cells such that they become inexcitable. Adenosine through activation of IKAdo hyperpolarizes these cells so that Na+ channels are reactivated, restoring excitability.29 This response contrasts with adenosine's effects in decremental atrial tissue and decremental APs (see above).16 In this case, resting membrane potential is also thought to be partially depolarized, and yet adenosine, instead of enhancing excitability, suppresses the action potential, making the cells inexcitable and resulting in conduction block. The cellular mechanisms governing adenosine's divergent effects in these 2 scenarios are not fully known but may have to do with the manner in which these cells develop partially depolarized resting membrane potentials. Ablation-induced thermal injury in normally polarized tissues is a reversible extrinsic/iatrogenic insult, producing partial membrane depolarization, which responds to adenosine by hyperpolarizing membrane potential toward the preablation potential, reestablishing Na+ conductance and excitability. In contradistinction, in decrementally conducting APs, it is inferred that decreased resting membrane potential is an intrinsic property of this atrial-like tissue. In this circumstance, adenosine-induced hyperpolarization has the opposite effect, decreasing action potential amplitude and excitability, culminating in conduction block, similar to the response seen in partially depolarized isolated atrial myocytes.9Adenosine is known to be a reliable tool to unmask the presence of latent preexcitation in nondecremental APs.30,31 It is also an effective means for judging the effectiveness of ablation of these pathways (either anterograde or retrograde).32 However, reemergence of transient pathway conduction with adenosine challenge after the AP has been putatively ablated is a demonstration of dormant conduction. Dormant conduction occurs in ≈12% of patients undergoing ablation of an AP.28 The conduction time over the AP in these patients is shorter than the conduction interval over the atrioventricular node, indicating that a rapidly conducting atrioventricular node does not obscure the presence of a slowly conducting AP. Adenosine-induced dormant conduction occurs during the bradycardic phase of adenosine effect, suggesting that adenosine's effects are a direct consequence of its actions on the AP and are not due to adenosine's late-phase sympathetic reflex. The presence of dormant conduction predicts recurrence of pathway conduction, which often leads to repeat ablation. An example of adenosine-induced dormant anterograde AP conduction is shown in Figure 6.Download figureDownload PowerPointFigure 6. Demonstration of dormant conduction over an anterograde atrioventricular (AV) accessory pathway with adenosine (ADO).A, Baseline preexcitation. The P-to-delta-wave interval was 97 ms. B, After ablation of the accessory pathway, the AV interval increased (PR interval, 130 ms) concomitant with loss of the delta wave. C, ADO (12 mg) caused AV block for 1 beat, followed by prolonged conduction over the AV node (PR interval, 167 ms), resulting in a narrow QRS complex. However, the following beat showed return of preexcitation (dormant conduction) with a P-to-delta-wave interval of 97 ms (*). D, Diagram illustrating the mechanism of dormant conduction. Left, The accessory pathway (AP) has a normal resting membrane potential of ≈−90 mV (preablation). Middle, After ablation, injury to the pathway causes relative depolarization and inexcitability because of inactivation of Na+ channels. Right, ADO hyperpolarizes the resting membrane potential of the accessory pathway (AP) via IKAdo, allowing reactivation of Na+ channels and transient return of excitability (preexcitation). AVN indicates atrioventricular node; RA, right atrium; and RVA, right ventricular apex. Other abbreviations as previously described. Reprinted from Spotnitz et al28 with permission. Copyright © 2014, American Heart Association, Inc.Atrial TachycardiaAdenosine has a singular capacity to provide insight into AT circuit dimension, probability of tachycardia location, and AT mechanism. To our knowledge, no other single agent possesses this capacity, nor requires <10 seconds to acquire this evidence.Adenosine Response Defines MechanismAlthough adenosine's effects on IKAdo in the atrioventricular node provide the basis for its clinical therapeutic role, activation of this current during AT has no known antiarrhythmic effect. Consistent with this finding, adenosine also has no known effect on macroreentrant or microreentrant AT.33–37 It is specifically adenosine's inhibitory effects on stimulated levels of cAMP that account for its signature effect on focal AT.The paradigm for diagnosing clinical, cAMP-mediated triggered activity is based in large part on the mechanism-specific effects of adenosine that were first established in the ventricle for outflow tract tachycardia.4,38 Triggered activity, like automaticity, depends on impulse initiation; however, in triggered activity, the arrhythmia is initiated and perpetuated by phase 4 delayed afterdepolarizations. Coincident with a delayed afterdepolarization achieving sufficient amplitude, a new action potential is triggered. Once this process becomes iterative, a sustained triggered rhythm results. On a cellular level, delayed afterdepolarizations are dependent on cAMP-stimulated intracellular calcium (Ca2+) overload, resulting in Ca2+-induced Ca2+ release from the sarcoplasmic reticulum and activation of electrogenic INCX, causing a net inward sodium current ITI during phase 4 of the action potential.Adenosine through its inhibition of cAMP-mediated increases in the slow-inward calcium current and its downstream inhibitory effects on sarcoplasmic reticulum Ca2+release, INCX and ITI, terminates focal arrhythmias caused by triggered activity.33–36 No other maneuver or agent reliably provides this mechanism-specific response, which is nearly 100% sensitive and specific.36 Other supportive findings consistent with triggered activity, although less specific, have been proposed as a part of a comprehensive electropharmacologic matrix.37Automatic AT occurs due to spontaneous depolarization during phase 4 and is facilitated by cAMP stimulation. These arrhythmias arise from a focal group of closely coupled cells, which are dependent on a variety of currents, including If and INCX. In contrast to triggered activity, automatic rhythms do not initiate or terminate with rapid pacing; however, they may manifest overdrive suppression. It is important to appreciate the distinction between adenosine's effects in cAMP-mediated automatic AT and in AT due to cAMP-mediated triggered activity. Adenosine transiently slows or suppresses but does not terminate adrenergically mediated automatic AT.33–36 Of note, catecholamine-mediated reentrant AT is insensitive to adenosine, similar to catecholamine-mediated reentrant ventricular tachycardia.39 Because catecholamine facilitation of reentrant tachycardia is usually mediated via effects on initiation rather than by perpetuation of the arrhythmia, and because adenosine is administered during the perpetuation phase of tachycardia, these arrhythmias do not terminate with adenosine.Adenosine Response: Implications for Circuit Dimension and LocationAT response to adenosine is informative for multiple reasons. Termination not only signifies the mechanism of the tachycardia but also indicates the relative circuit dimension, that is, focal, and also identifies the likely sites of AT origin. This has obvious implications for expediting mapping and ablation of AT. The overwhelming majority of all focal forms of de novo AT terminate with adenosine,36 with focal reentry and automaticity accounting for a relatively small percentage of all focal ATs. The implications of adenosine termination are, therefore, broad. It suggests that mechanistically triggered activity is a far more ubiquitous arrhythmia than thought previously. Underestimation of triggered activity's role is explicable since there is a proclivity to interpret phenomena in the context of existing paradigms. These paradigms are in turn dependent on the type of phenomena that can be measured and quantified. In a field where the concepts of reentry were established a century ago, and where there is a direct means of confirming the diagnosis by activation mapping and entrainment, there is an inclination to first consider reentry as the arrhythmogenic mechanism of an AT until proven otherwise. This was for good reason because, before the recognition of adenosine's utility, there was no specific or sensitive means by which to establish the diagnosis of triggered activity. Adenosine has provided insight into a clinical mechanism of arrhythmia that previously had been considered a bench lab curiosity. Armed with this knowledge, it can be concluded that any AT that is sensitive (termination or suppression) to adenosine is focal in origin. These arrhythmias are further characterized by discrete electrograms at the site of origin and centrifugal activation. Triggered AT is differentiated from automatic AT by the type of response to adenosine (termination versus transient suppression) and the response to programmed stimulation (initiation/termination versus overdrive suppression).Another insight gained from adenosine termination of AT is the probable site of tachycardia origin. These particular focal ATs are clustered in relatively few discrete regions. The most common sites are the periannular tricuspid region (including para-Hisian and the noncoronary cusp), mitral annulus, and crista terminalis.34–36,40,41 Other sites include the right atrial appendage and the right and left atrial septum. This has practical utility as shown in Figure 7. In this example, eccentric retrograde atrial activation during tachycardia suggested the possibility of a concealed left-sided atrioventricular pathway; however, the response to ventricular overdrive pacing (V-A-A-V response) confirmed a diagnosis of AT. Termination of the AT with adenosine established 2 critical points: (1) the arrhythmogenic circuit was focal and (2) based on eccentric activation of the left atrium, the circuit was likely localized to a focal hotspot, that is, the mitral annulus.Download figureDownload PowerPointFigure 7. Termination of atrial tachycardia (AT) with adenosine facilitates in classifying AT circuit dimension and origin.A, Narrow complex tachycardia with eccentric activation terminated with adenosine after ventricular activation, findings consistent with AT. This was confirmed by a V-A-A-V response during ventricular overdrive pacing. The response of tachycardia to adenosine was consistent with a focal AT that was due to triggered activity. Furthe