MASOOD AKHTAR, MD, PATRICK J. TCHOU, MD, and MOHAMMAD JAZAYERI, MD

Animal data suggest that cardiac arrhythmias can result from a variety of mechanisms. In clinical set- tings, arrhythmias that are easily initiated and termi- nated with programmed electrical stimulation are of- ten designated as reentry tachycardias. However, proof of reentry is contingent upon demonstration of the entire circuit; this relation has been proposed for arrhythmias associated with large circuits, such as those seen in the Wolff-Parkinson-White syndrome. Reentry has also been proposed as the mechanism responsible for a variety of other tachycardias, in- cluding bundle branch and atrioventricular nodal re- entry tachycardia, permanent junctional reentrant tachycardia, reentry tachycardia associated with nodoventricular Mahaim fibers and inducible atrial and ventricular tachycardia. Documentation of trig- gered rhythms as the mechanism responsible for

clinical arrhythmias has been even more difficult. Examples of arrhythmias resulting from triggered activity may include those associated with digitalis toxicity arising from the atria, the atrioventricular junction or the ventricles. Clinical arrhythmias due to triggered activity in the absence of digitalis have also been described. Cardiac arrhythmias that can- not be induced by electrical stimulation are presum- ably due to normal or abnormal automaticity. Exam- ples of normal automaticity in the human heart are sinus rhythm and junctional and idioventricular es- cape rhythms. Tachycardias by abnormal automa- ticity have seldom been investigated for the purpose of documenting the mechanism and therefore the limited data available make it difficult to draw any final conclusions.

(Am J Cardiol 1988;81:gA-1gA)

A variety of mechanisms for the development of car- diac arrhythmias have been identified in animal mod- els.l-7 However, the only mechanism that has been intensively investigated in the intact human heart is reentry. Even this proposed mechanism of clinical tachycardia has been questioned in many cases. In this report, our current knowledge of the mechanisms re- sponsible for cardiac arrhythmias encountered in clin- ical settings is reviewed. Only sustained regular tachy- cardias of clinical significance are considered, and arrhythmias such as atria1 and ventricular fibrillation are not discussed.

Most of our knowledge about the mechanism re- sponsible for clinical tachycardias has been derived from the results of programmed electrical stimulation (PES) in patients with recurrent symptomatic arrhyth- mias.8-20 Transient asymptomatic arrhythmias have not been evaluated in great detail because they can seldom be tested with PES. The usefulness of PES may be further limited because patients with arrhythmias

From the Natalie and Norman Soref and Family Electrophysiol- ogy Laboratory, University of Wisconsin-Milwaukee Clinical Campus, Mount Sinai Medical Center, Milwaukee, Wisconsin.

Address for reprints: Masood Akhtar, MD, Electrophysiol- ogy Laboratory, Mount Sinai Medical Center, 950 North Twelfth Street, Milwaukee, Wisconsin 53233.

9A

not considered traditionally inducible may not be re- ferred for electrophysiologic evaluation. For these rea- sons, it is possible that the overall incidence of reentry as a mechanism for human arrhythmias has been somewhat overestimated. Nevertheless, patients re- ferred for recurrent symptomatic sustained tachycar- dias generally do have inducible arrhythmias when tested with PES. In this report, inducible tachycardias are discussed first, followed by tachycardias not in- ducible with PES and often ascribed to normal or ab- normal automatic mechanisms.

Inducible Arrhythmias At present, data suggest that inducible arrhythmias

can be broadly attributed either to reentry or to after- depolarization. Among the latter, delayed afterde- polarization has been implicated more often than so- called early afterdepolarization as the cause of sus- tained arrhythmias. Therefore, for practical purposes, a distinction between reentry and triggered activity due to delayed afterdepolarization has become impor- tant.21 It has been relatively easy to distinguish be- tween the 2 in animal models; however, a convincing demonstration of arrhythmia mechanisms in the clini- cal setting has been difficult for a number of rea- sons.21.22 Reentry is currently accepted as a mecha- nism only when the entire circuit can be mapped, and

IOA A SYMPOSIUM: ARRHYTHMIA THERAPY-CONTROVERSIES, DIRECTIONS AND CHALLENGES

it can be shown that conduction along all segments of the circuit is essential for initiation and continuation of the arrhythmias.

Cardiac arrhythmias with well-defined reentry circuits: The circus movement reentry tachycardia in Wolff-Parkinson-White syndrome (i.e., both orthodro- mic and antidromic tachycardia using large reentry circuits] provides the most convincing examples of re- entry as a mechanism for causing arrhythmia in hu- mans.11J2J7 Orthodromic tachycardia clearly requires intact atrial, anterograde atrioventricular (AV) nodal, His-Purkinje system, intraventricular and retrograde accessory pathway conduction for the process to con- tinue. Similarly, during antidromic tachycardia, anter- ograde accessory pathway, intraventricular, retro- grade normal pathway and intraatrial conduction are necessary. A somewhat similar tachycardia involving another accessory pathway in a retrograde direction may be more common than previously thought (Fig. 1).

Aside from the various electrophysiologic manipula- tions that can be performed to validate the foregoing points, the fact that surgical resection of accessory pathways abolishes both types of reentry tachycardias lends credence to the theory that accessory pathways are an essential component of the reentry circuit in circus movement tachycardia.

The only other large circuit reentry that has permit- ted demonstration of the routes of impulse propagation is the so-called macroreentry in the His-Purkinje sys- tem or bundle branch reentry.*sJO Bundle branch re- entry can be demonstrated as a single beat in most patients with normal intraventricular conduction, and the reentry circuit can be identified by means of re- cordings from the His bundle and bundle branches (Fig. s].lg Sustained tachycardia of this type can be induced in the laboratory in approximately 5% of pa- tients with diseased His-Purkinje systems who present with sustained monomorphic ventricular tachycardia

FIGURE 1. Circus movement tachycardia in a patient with 2 accessory pathways. The tracings in each panel, from top to bottom, are surface electrocardiographic leads 1, 2, V,, high right atrium (HRA), coronary sinus (CS), His bundle (HB) electrogram and time lines. A similar format is used in subsequent tracings. Pane/A shows preexcitation during a reference sinus beat. Atrial premature stimulation (AZ) from the HRA (panel B) initiates a wide QRS tachycardia with anterograde conduction over a left free wall accessory pathway and retrograde conduction through an anteroseptal accessory pathway or normal pathway, or both, as suggested by the atrial activation sequence. The direction of conduction in the 2 pathways is reversed in pane/ Cduring the initiation of another preexcited circus movement tachycardia with a single premature beat delivered in the CS. Small arrows depict anterograde activation of the HB, which is incidental, since the reentry is maintained by conduction delays along the 2 accessory pathways. Peipendicular lines are drawn in panels 6 and Cfrom the point of earliest atrial activation. The designations S,, A,, H, and VI represent stimulus artifact, atrial, HB and ventricular electrograms during the basic drive, whereas Sz, Ar and V2 depict corresponding deflections with premature beats. Ae = atrial reciprocal response.

January 15, 1988 THE AMERICAN JOURNAL OF CfiROlO~OGY Volume 61 IIA

(Fig. 3). Recent demonstration that selective ablation of the right bundle branch (leaving intact AV conduction) can cure this type of clinical arrhythmia supports, the existence of the proposed circuit and the hypothesis that bundle branch reentry does occur as a sustained symptqmatic tachycardia in humans.23J4

It is difficult to define the circuit in arrhythmias involving rkentry because of a leading circle and in arrhythniias involving a relatively small area-l Obser- vations made during arrhythmias caused by .known reentry mechanisms have therefore been used to indi- rectly extrapolate the mechanisms responsible for ar- rhythmias when .mappitig of ‘the circuit was not possi- ble. The’se indirect criteria for determination 6f tachycardja mechanisms are outlined.

1. Relation between cycle length, coupling interval and tachycardia induction: The various mechanisms that cause tachyarrhythmia have been well character- ized in animal models, and the emergent criteria are being used to clarify the mechanisms of arrhythmia in humans.

The duration of the basic cycle length appears to be critical for the initiation of delayed afterdepolariza- tion; when the basic cycle length is long, induction of delayed afterdepolarization is difficult. Isolated single premature beats seldom initiate triggered rhythms from delayed afterdepolarization bedause the ampli- tude of afterdepoltirization is more strongly influenced by the duration of the basic cycle length than by the coupling interval of a premature beat. Thus, a tachy-

1

FIGURE ?. Macroreentry His-Purkinje system. A single premature beat (Sz) delivered in the right ventrjlcle is followed by a nonstimulated complex; this complex is preceded by a His and right bundle activaiion sequence very similar !o that seen during the reference sinus beat. The activation sequence shown suggests His bundle (Hg) activation by way of the left bundle, followed by ariterograde conductipn‘along the’rlght bundie branch, i.e., along the previously proposed circuit of reentry. HRA = high right atrium: RB = pro$m+ right’bundle potential; RB’ = distal right bundle potential.

FIGURE 3. Sustained bundle branch reentrant tachycardla. During the ventricular tachycaldia shown, retrograde activation of the His bundle (HB) ocqurs by way of the left bundle and anterograde conduction occurs along the rjght bundie (RB), as suggested by the HB-RB aCti&iOn sequence. Overdrive pacing terminates the ventricular tachycardia when the last paced beat does nit reach the HI? bundle. The large hOfkOnfa~ arrows point toward .the HV, H-H, and RB-RB va!ues listed, whereas the s&/ arrows in the bottom tracing depict RB poteqtials.

12A A SYMPOSIUM: ARRHYTHMIA THERAPY-CONTROVERSIES, DIRECTIONS AND CHALLENGES

cardia that begins with a single premature beat during spontaneous rhythms or a long-paced basic cycle length would favor reentry. Although AV nodal reen- try, intraatrial reentry and orthodromic tachycardia can often be induced by single premature beats, most forms of ventricular tachycardia cannot be initiated this way. Hence, a lack of inducibility under such cir- cumstances does not rule out reentry as the mecha- nism. However, when the basic cycle length is short and the arrhythmia follows a series of prematur’e beats, tachycardias from either of the 2 mechanisms can be induced.

2. Return cycle: It has been suggested that the trig- gered rhythm from delayed afterdepolarization main- tains a direct relation with both the basic cycle length and the coupling interval of the initiating beat.21J2J5 In

ms 700

600

600

;o’ 5 500

400

00

0 a0

0 0

0

OOOO 0

‘ I !

SOQ 600 700m CL

FIGURE 4. Initiation of ventricular tachycardia due to triggered activity. The return cycle after teimihation of atrial pacing (VP&) and ventricular pacing (VPC,) is plotted against progressively shorter paced cycle lengths (CL). It is clear that the return cycle has a direct relation with the cycle length of pacing initiating the rhythm. (Reproduced With permission from J Clin Invest.25)

other words, the return cycle [i.e., the interval between the last paced beat and the first tachycardia beat) var- ies directly with basic cycle length or coupling inter- val, or both (Fig. 4). In reentry, on the other hand, although the duration of the basic cycle length seems to have an inconsistent effect on tachycardia induc- ibility, an inverse relation between the coupling inter- val and the return cycle can often be demonstrated (Fig. 5).

Introduction of isolated premature beats during re- entry tachycardia with an excitable gap can produce varying effects, but seldom results in a return cycle shorter than the cycle length of tachycardia (Fig. 6).26 Such a pattern of decreasing return cycle length is more characteristic of a triggered rhythm due to digi- talis toxicity than of a rhythm due to reentrant excita- tion.27 A reentrant circuit without an excitable gap would be difficult to evaluate on the basis of the return cycle length.

3. Conduction delays and block: Because most doc- umented reentry phenomena are associated with con- duction delay, its association with the onset of tachy- cardia is used as indirect evidence that reentry is the underlying mechanism. Although conduction delays can often be demonstrated for AV nodal reentry and orthodromic tachycardia, they are seldom document- ed in atria1 or ventricular tachycardia. The progressive conduction delays and intraatrial -block and reentry

300

250

200

m.sec.

150

100

50

ERP

VM

fk .A

VCL= 700

9 % Ret Block 0 0 HPS

300 350 m. sec. Vl v2

FIGURE 3. Return cycle during bundle branch reentry. Progressive retrograde (Ret) delays in the left bundle branch system are seen as ttie VlV2 interval is shortened at a paced ventricular cycle length (VCL) of 700 ms. Note the reciprocal relation between V1V2 and the ieturn cycle (V,V,). There is also a reciprocal relation between the retrograde (Le., V2H2 by way of the left bundle) and anterograde (H2Vs along the right bundle) conduction times in the reentry circuit. ERP = effective refractory period; UPS = His-Purkinje system; VM = ventricular myocardium.

January 15, 1988 THE AMERICAN JOURNAL OF CARDIOLOGY Volume 61 13A

shown in Figure 7 strongly support intraatrial reentry as the mechanism for atria1 reexcitationz8 However, this has rarely been shown to precede sustained atria1 or ventricular tachycardia. At best, fractionated elec- trograms have been recorded on occasion from pre- sumed sites of arrhythmias.2g This provides weak sup- port for a causal relation since arrhythmias could conceivably arise from remote sites due to mecha- nisms unrelated to fractionated electrograms.

Onset of tachycardia that coincides with the pro- duction of a unidirectional block strongly suggests re- entry. For example, a block of atria1 impulse in the accessory pathway or ventricular impulse in the His- Purkinje system often coincides with the onset of or- thodromic tachycardia. Unfortunately, this relation cannot be shown in the intact human heart with either atria1 or ventriculr arrhythmias. In AV nodal reentry, a sudden jump in intranodal conduction time is often associated with the onset of tachycardia and is consid- ered to represent block in the fast pathway and a switch of conduction from fast to slow [Fig. 8).30 Be- cause some doubt has been cast on the exact role of retrograde pathways in so-called AV nodal reentry, the relevance of a jump in AV nodal conduction to

+ Return Cycle

(mr)

Q

FLAT

+ + Coupling Interval (ms)

DECREASING

INCREASING

MIXED (F+I)

FIGURE 6. Return cycle during resetting of ventricular tachycardia. Depicted are patterns of return cycle from 32 patients (37 tachycar- dias) after rest with single or double premature stimuli during ven- tricular tachycardia. All except the decreasing patterns were seen. The decreasing pattern has been observed in digitalis-induced ven- tricular tachycardia, presumably induced by triggered delayed af- terdepolarizations. F = flat; I = increasing. (Reproduced with per- mission from Circulation.26)

FIGURE 7. lntraatrial reentry. Panel A depicts marked conduction delay between low right atrial on His bundle electrogram (HBE) and high right atrial (HRA) sites of recording. An intraatrial block is seen in pane/ B. In pane/ C, intraatrial conduction resumes at a short cou- pling interval (gap phenomenon in the atrium), and the low atrium is reexcited. VCL = ventric- ular cycle length. (Reproduced with permission from Circulation.28)

14A A SYMPOSIUM: ARRHYTHMIA THERAPY-CONTROVERSIES, DIRECTIONS AND CHALLENGES

400 --

RRP

350.. 6

M. SEC. ERP

300 -. ATRlUh

250

200

150

100

50 I+ 200

ANT. R.P.: AC L; 750

Echo

Zone ,

*

0

0

0

00 00000

4

360

0 Vl vi

l HlH2

0 S2H2

. 00

000 00

SI SP (AI Ai’) hi SEC.

FIGURE 8. Initiation of atrioventricular (AV) ncidal reentry. Progres- sive AV nodal delays (A2Hz) can be seen as the AlA intervals are shortened. A sudden upward shiit in S2H2 and HIHz curves occurs at an A,A; of 380 ms, which coincides with initiation of AV nodal reentraht tachycardia. This finding has been iriterpreted as indica- ilve of block of the fast pathway and a shift of anterograde conduc- tlori to the slow patliwtiy. ACL = atrial cycle length; Ant. R.P. = anterograde refractdry period; l%p = effective refractory period; RRP = relative refractory period.

actual reentry is uncertain at pre.senL31 Therefore, pro- gressive conduction delay, block, or both, that coin- cides with the onset of tachytirrhythmia strongly sug- gest reentry as the mechanisin but do not prove it.

4. Entrainment and progressive fusion: Since the demonstratiqn of atria1 flutter entrainment by Waldo et a1,32-34 entrainment with overdrive pacing has been attempted in many other forms of tachycardia (Fig. 9). In essence, the concept implies that a reentry circuit with an excitable gap can be engaged in such a way that the rate of revolution in the reentry circuit follows the paking rate. At the termination of pacing, the tachy- cardia resumes at the original rate (Fig. 9). Depending on the site of pacing, progressive fusion between the activation front initiated by the paced beat and the exit of entrained impulse from the circtiit can be demon- strated with the acceleration of pacing rate. At a given pacing rate, however, the degree of fusion remains constant. When these observations are coupled with tachycardia termination coincident with block of paced impulse in an orthodromic direction, it is con- sidered evidence of Peentry.33 Hbwever, none of the foregoing observations may be demonstrable in a re-

entry circuit without an excitable gap. Furthermore, all features of entrainment to termination may be difficult to show in a giveri reentry circuit, even with an excit- able gap.

In large tiircuits, such as those associated with or- thodromic and antidromic tachycardia, many of the criteria pointed out by Waldo et a133 can be shown. Extrapolating this tpe of information to other circuits, such as those in ventricular tachycardia, should be done with caution. Figure 10 illustrates schematically how entrainmept and fusion might be observed fn a tachycardia induced by a nonreentrant mechanism. This process is herein explained.

Assuming that an abnormal automatic rhythm ex- ists in the diseased portion of the myocardium, the initial impulse may block in 1 direction and proceed in the other, thus setting up ati activation sequence that could closely simulate reentry. A linking phenome’non resulting from collision of 2 impulses within the site of initial block could sustain the same sequence of activa- tion.35 In other words, each automatic tachycardia impulse may be forced to follow the same route as previous impulses because of previous impulses ap- proaching from the other direction. By pacing tit a site away from the point of initial breakthrough, impulses could advance along the committed route, emerge at the exit point and then fuse with the next paced im- pulse. Termination of pacing could result iti reemer- gence of tachycardia from the nonreentratit mecha- nism. During the so-called entrainment, the original tachycardia could retiain concealed. Thus, what is interpreted as tachycardia entrainment and fusion during pacing is simply a collision between the paced impulse emerging from the area of abnormal myocar- dium and antidromic propagation from the paced impulse.

So-called tachycardia entrainment is actually a misnomer because during entrainment only the paced impulses are propagating, and there is no spontaneous tachycardia impulse. This interaction between ortho- dromic and antidromic wavefronts initiates a form of linking phenomenon. The linking phenomenon can be denionstrated in large circuits, both in tachycardia and in nontachycardia settings, and conceivably could oc- cur in small circuits as well (Fig. 9 and 11).35 The i types of linking phenomenon previously described have somewhat different electrophysiologic bases (Fig. 12). The first type, linking by interference, is char- acterized by an impulse that actually blocks but in its wake leaves refractoriness, which in turn results in the block of the next impulse approaching from the oppo- site directiqn (Fig. 11 and 12, panel B). The second type of linking is characterized by the actual collision pf orthodromic and antidromic impulses. Otherwise, the impulse propagation is not limited by refractory tissue (Fig. 9 and 12, panel C). Whereas linking by collision would explain the so-called tachycardia entrainment atid progressive fusion, linking by interference may play a role in abor;tive reentry and tachycardia termi- nation. In so-called entrained tachycardia, a block in the orthodromic direction alone will set up an antidro- mic reentry from the paced impulse unless the ortho-

January 15, 1988 THE AMERICAN JOURNAL OF CARDIOLOGY Volume 61 15A

FIGURE 9. Entrainment of macroreentrant ventricular tachycardia. During a sustained bundle branch reentry with a cycle length of 310 ms, right ventricular overdrive pacing (CL 270) advances the His bundle (HE) potential by engaging the right bundle in a retrograde fashion and, at the same time, proceeding transseptally to collide with orthodromic impulse, resulting in a fusion complex. The termination of pacing is followed by a resumption of the original tachycardia rate. The diagrams at the bottom show sustained circuit (A), entrainment with fusion (B) and resumption of tachycardia when pacing is Interrupted (C). LB = left bundle; RB = right bundle; VM = ventricular muscle. (Reproduced with permission from Circulation.35)

dromic block sets up an area of refractoriness through which the antidromic impulse fails to propagate, thus terminating the tachycardia.

5. Response to different classes of drugs: Based on the available information on the electrophysiologic properties of antiarrhythmic drugs, it appears unlikely that a particular response to a given agent will clarify the underlying mechanism.7 Most agents have numer- ous effects; this makes the interpretation of response difficult, particularly in clinical settings7 Even in the case of triggered activity due to digitalis toxicity, which can be abolished by verapamil, this effect cannot be construed as demonstrating triggered activity because a variety of class I agents can produce the same results. Similarly, ,LLadrenergic blocking agents may also pro- duce nonspecific responses.7 Since catecholamines can augment delayed afterdepolarizations and im- prove conduction in depressed areas as well as en- hance spontaneous phase 4 depolarization, P-blocking agents may be effective against arrhythmias resulting from automaticity, triggered activity or reentry.7

In some cases, intact bidirectional conduction (i.e., orthodromic or antidromic tachycardia and AV nodal reentry) has been shown to be essential for initiating and sustaining tachycardia. A unidirectional or bidi- rectional drug-induced block that eliminates the ar- rhythmia provides support for reentry as a mechanism (Fig. 13). However, this response by itself does not

( Non reentrant VT)

FIGURE 10. Entrainment with fusion (nonreentrant ventricular tachycardia [VT]). These diagrams show 1 possible scenario in which an automatic tachycardia can be associated with an activa- tion sequence simulating reentry (/eff panel). Overdrive pacing (S) remote from the exit points of VT results in fusion and orthodromic penetration and engagement of the area of VT origin. (See text for more details.)

prove that reentry is the mechanism responsible, since a depressant effect on conduction may also be associ- ated with suppression of other arrhythmia mecha- nisms. Obviously, in atria1 and ventricular tachycardia circuits, the effects of specific drugs are more difficult to assess in terms of their relevance to a specific mech- anism. Traditionally, however, @- and calcium chan- nel blocking agents have been less effective than class I agents in preventing inducible sustained monomor- phic ventricular tachycardia.36 These observations do

16A A SYMPOSIUM: ARRHYTHMIA THERAPY-CONTROVERSIES, DIRECTIONS AND CHALLENGES

suggest that reentry rather than triggered activity is the common cause of such tachycardias.

Drug-induced aggravation in the form of incessant tachycardia, which is most often produced by class I agents (particularly class IC), may provide some of the most convincing support for reentry as the mechanism of ventricular tachycardia associated with old myocar- dial infarction. Although incessant tachycardia is not common, less severe forms of drug-related aggrava- tion, such as easier initiation and more difficult termi- nation, are not uncommon in the laboratory in patients with monomorphic ventricular tachycardia. It is not clear whether such a response to a class I agent can also occur in arrhythmias due to other mechanisms.

6. Effect of local manipulation: The ability to termi- nate a tachycardia (by local pressure, cooling, etc.) at any point along the reentry excitation pathway pro- vides conclusive evidence that reentry is the mecha- nism responsible. The effect of local manipulation must be tested at several points along the presumed reentry pathway, since isolated manipulation may ter- minate an arrhythmia induced by any mechanism if the site of origin is mechanically altered. Furthermore, a reentry tachycardia that is terminated by localized manipulation of a critical point (i.e., the accessory pathway or the exit site of a ventricular tachycardia circuit] may not be terminated by manipulation at oth-

er sites, because the advancing wavefront simply goes around the point of local manipulation and advances through an alternate route. Use of an alternate route, however, often results in a slowing of the tachycardia rate by increasing the revolution time. Thus, although a slowing of the tachycardia rate or termination with local manipulation supports reentry as a mechanism, the inability to terminate the tachycardia through local manipulation does not rule out reentry.

A variety of other findings, including site specificity for induction or termination, overdrive acceleration or abrupt termination and rates of tachycardia, are not very useful for distinguishing reentry tachycardias from other triggered phenomena in clinical settings, However, determining the specific mechanism for a clinical arrhythmia involves the consideration of sev- eral criteria and is not done on the basis of a single finding. Collectively, many of the foregoing observa- tions provide a fairly accurate assessment of the mech- anism of tachycardia in individual patients.

Table I lists those clinical arrhythmias that can be ascribed to reentry in order of decreasing certainty. Most of the well-defined reentry circuits are located within the AV junction and tend to be relatively large. However, these well-established reentry tachycardias sometimes cannot be initiated when the conditions for reentry are not ripe. Therefore, inability to induce a

1%

FIGURE 11. Linking by interference. in a patient with preexcitation, a train of ventricular stimuli (S&) is programmed to follow an atriai drive (S,S,). Pane/A, retrograde His-Purkinje system delays occur (S2H2) with the second and third paced ventricular beats. His-Purkinje system accomodation follows. At a shorter SzS2 of 300 ms (pane/ B), the third Sz blocks in the His-Purkinje system conducts to atria through the accessory pathway. The impulse then blocks in the orthodromic direction in the His-Purkinje system due to refractoriness created by a previous impulse during its retrograde block. The next paced Ss also blocks in the His-Purkinje system because the latter is not recovered after anterograde penetration. Each subsequent S2 follows the same committed route, and the sequence of S2 + A2 -+ H2 continues indefinitely. Other abbreviations as before. (Reproduced and modified with permission from Circuiation.35)

January 15, 1988 THE AMERICAN JOURNAL OF CARDIOLOGY

FIGURE 12. Two forms of linking phe- nomena. Schematic representation of a generalized linking phenomenon. Panel A depicts a hypothetical macroreentry circuit into which successive impulses (*) enter and preferentially traverse 1 limb as a result of persistent functional block (shadedregion) in the contralater- al limb. Panels B and C show 2 distinct mechanisms in which the functional block can be dynamically maintained; I3

each pane/ is a “blow-up” of the region An-, A, An+1 of block as it is invaded by successive \ \ \ (n-2, n-l, n, etc.) anterograde and retrograde Impulses over time. Panel B

l **

shows impulse interference, whereas C / / / depicts impulse collision. Other abbrevi- I? ations as before. (Reproduced with per-

n-l Rn Rn+l

Volume 6 1 17A

mission from Circulation.35)

TIME

FIGURE 13. Effect of drugs on ret- rograde conduction and abolition of atrloventricular nodal reentry. Panel A shows the initiation of sustained atrioventricular nodal reentry tachycardia during con- trol. A 1:l ventriculoatrial con- duction is noted at a paced cycle length of 300 ms (pane/B) before intravenous administratlon of pro- pranolol. After administration of a small amount of propranolol, a single atrial echo (AE) is initiat- ed, the next impulse blocks in a retrograde fashion (i.e., H but no Ae), and the tachycardia can no longer be sustained (pane/ C). Ventricular pacing in pane/ D shows onset of ventriculoatrial block at a relatively long-paced cycle length of 600 ms. Drug-in- duced abolition of tachycardia coincident with depressant effect on retrograde conduction sug- gests the participation of a retro- grade pathway in the tachycardia and lends support to reentry as the mechanism.

A CONTROL

1 AU

2 u VCL:300

A A A

VA* 115

C PROPRANOLOL

1 A h 2 A-_A A-A

HB

D

10A A SYMPOSIUM: ARRHYTHMIA THERAPY-CONTROVERSIES, DIRECTIONS AND CHALLENGES

TABLE I Clinical Arrhythmias Due to Reentry

Orlhodromic and antidromic supraventricular tachycardia associated with Wolff-Parkinson-White syndrome

Bundle branch reentry Reentry using Mahaim fibers Permanent junctional reentrant tachycardia Atrioventricular nodal reentry Sustained monomorphic ventricular tachycardia lntraatrial reentry tachycardias

TABLE II Clinical Arrhythmias Due to Triggered Activity

Rhythms and tachycardia related to digitalis toxicity arising in the atria, atrio- ventricular junction, fascicle or ventricle

Accelerated junctional and idioventricular rhythms Certain forms of ventricular tachycardia

TABLE Ill Clinical Arrhythmias Due to Abnormal Automaticlty

Multifocal atrial tachycardia Paroxysmal junctional ectopic tachycardia Some forms of ventricular tachycardia

tachycardia does not rule out reentry. Cardiac arrhyth- mias that may be due to triggered activity in the clinical setting have been difficult to define but may include those in which accelerated rhythms and tachycardias due to digitalis toxicity arise in the atrium, the AV junction or the ventricle. 37-3g In the absence of digitalis toxicity, a variety of cardiac arrhythmias have been ascribed to triggered activity, but proving the precise mechanism responsible remains difficult.40z41 Table II lists some possible examples.

Noninducible Arrhythmias Characterizing the rhythms and tachycardias that

cannot be induced with PES has been difficult. Such arrhythmias are generally termed “automatic.“42 Per- haps the only convincing examples of such arrhyth- mias arising in the face of normal automaticity are sinus rhythm, escape junctional and idioventricular rhythms. Normal automaticity has been defined as rhythms that cannot be initiated or terminated but can be overdrive suppressed.

Demonstration of abnormal automaticity, which in- cludes rhythms that cannot be initiated, terminated or overdrive suppressed, has been equally difficult.43 It is conceivable that transient arrhythmias, particularly those associated with high catecholamine levels, are due to such mechanisms but are seldom studied for better definition. Table III lists some examples of clini- cal arrhythmias that are thought to be due to automa- ticity. However, such considerations are based on the limited data available.

References 1. Allessie MA, Bonke FIM, Schopman FJG. Circus movemeflt in rabbit atria1 muscle (IS c mechanism of tachycardia III. The “leading circle” concept: o new model of circus movement in cardiac tissue without the involvement of an antomicol obstacle. Circ Res 1977;41:9-18. 2. Wit AL, Hoffman BF, Cranefield PF. Slow conduction and reentry in the

ventricular conducting system. I. Return extrosystole in canine Purkinje fi- bers. Circ Res 1972;3&1-10. 3. Wit AL, Cranefield PF, Hoffman BF. Slow conduction and reentry in the ventricular conducting system. II. Single and sustained circus movement in networks of canine and bovine Purkinje fibers. Circ Res 1972;30:11-22. 4. Wit AL, Cranefield PF. Triggered and automatic activity in the canine coronary sinus. Circ Res 1977;41:435-445. 5. Antzelevitch C, Jalife J, Moe GK. Characteristics of reflection QS a mecha- nism of reentrant arrhythmias and its relationship in parasystole. Circulation 1980;61:182-191. 6. Moak JP, Rosen MR. Induction and termination of triggered activity by pacing in isolated canine Purkinje fibers. Circulation 1984;69:149-362. 9. Frame LH, Hoffman BF. Mechanisms of tachycordia. In: Surawicz B, Pratap Reddy C, Prystowsky EN, eds. Tachycardias. Massachusetts: Martinus Nijhoff Publishing, 1984:7-36. 6. Durrer D, Schoo L, Schuilenburg RM, Wellens HJJ. The role of premature beats in the initiation and termination of suproventricular tachycardia in the Wolff-Parkinson-White syndrome. Circulation 1967;36:622-644. 9. Goldreyer BN, Damato AN. The essential role of atrioventriculor conduc- tion delay in the initiation of paroxysmal supraventricular tachycardia. Cir- culation 1971;43:679-687. 10. Akhtar M, Damato AN, Ruskin JN, Batsford WP, Reddy CP, Ticzon AR, Dhatt MS, Games JA, Calon AH. Antegrade and retrograde conduction char- acteristics in three patterns of paroxysma atrioventricuior junctional reen- trant tochycardia. Am Heart J 1978;95(1):22-42. 11. Wellens HJJ, Durrer D. The role of an accessory atrioventriculor pathway in reciprocal tachycardia. Circulation 1975;52:58-72. 12. Gallagher JJ. Pritchett ELC, Sealy WC, Kasell J, Wallace AC. The reexcita- tion syndromes. Prog Cardiovasc Dis 1978;20:285-327. 13. Wellens HJJ, Lie KI, Durrer D. Further observations on ventricular tachy- cordio (IS studied by electrical stimulation of the heart. Circulation 1974; 49547-653. 14. Josephson ME, Horowitz LN, Farshidi A, Kastor JA. Recurrent sustained ventricular tachycardia. I. Mechanisms. Circulation 1978;57:431-440. 15. Gallagher JJ. Variants of pre-excitation: Update 1984. In: Zipes DP, Jolife J, eds. Cardiac Electrophysiology and Arrhythmias. Orlando, FL: Crune @r Stratton. 1985:419-433. 16. Gallagher JJ. Sealy WC. The permanent form of junctional reciprocating tochycordio: further elucidation of the underlying mechanism. Eur J Cardiol 1978;8:413-430. 17. Bardy GH, Packer DL, German LD, Gallagher JJ, Pre-excited reciprocat- ing tachycardio in patients with Wolff-Pa and mechanisms. Circulation 1984;70:377-391. 16. Zipes DP, Foster PR, Troup PJ, Pedersen DH. Atria1 induction of ventricu- lar tachycardio: reentry versus triggered automaticity. Am J Cordiol 1979; 44:1-8. 19. Akhtar M, Gilbert C, Wolf F, Schmidt D. Reentry within the His-Purkinje system: elucidation of reentrant circuit utiIizing right bundle and His bundle recordings. CircuIation 1978;58:295-304. 20. Touboul P, Kirkorian G, Atallah G, Moleur P. Bundle branch reentry: a possible mechanism of ventricular tachycardio. Circulation 1983;67:674-680. 21. Rosen MR, Reder RF. Does triggered activity have (7 role in the genesis of cardiac arrhythmias? Ann Intern Med 1981;94:794-801. 22. Rosen MR. Is the response to programmed electrical stimulation diagnos- tic of mechanisms for arrhythmias? Circulation 1986;73:18-27. 23. Touboul P, Kirkorian G, Atallah G, Lavaud P, Moleur P, Lamaud M, Mathieu MP. Bundle branch reentrant tachycordio treated by electrical oblo- tion of the right bundle branch. JACC 1986;7:1404-1409. 24. Denker ST, Mahmud R, Tchou P, Jazayeri M, Al-Bitar I, Akhtar M. Demonstration of catheter ablative technique for control of ventricular tachy- cardia due to macro-reentry within the His-Purkinje system (abstr). JACC 1986;7:243. 25. Sung RJ, Shapiro WA, Shen EN, Morady F, Davis ]. Effects of verapami1 on ventricular tachycardios possibly caused by reentry, automaticity and triggered activity. J CIin Invest 1983;72:350-360. 26. Almendral JM, Stamato NJ, Rosenthal ME, Marchlinski FE, Miller JM, Josephson ME. Resetting response patterns during sustained ventricular tachycardio: relationship to the excitable gap. Circulation 1986;74:722-730. 27. Gorgels AP, Beckman HD, Brugada P, Dassen WR, Richards DA, Wellens HJJ. Extrastimulus-related shortening of the first postpacing interval in digi- talis-induced ventricular tachycordio: observations during programmed elec- tricai stimulation in the conscious dog. JACC 1983;1:840-857. 26. Akhtar M, Caracta AR, Lau SH, Gilbert CJ, Damato AN. Demonstration of intro-atria1 conduction delay, block, gap and reentry: (I report of two cases. CircuIation 1978;58:947-955. 29. losephson ME, Wit AL. Fractionated electrical activity and continuous electrical activity: fact or artifact. Circulation 1984;70:529-537. 30. Rosen KM, Mehta A, Miller RA. Demonstration of dual atrioventricuIar nodal pathways in man. Am f Cardiol 1974;33:291-294. 31. Ross DL, Johnson DC, Denniss AR, Cooper MJ, Richards DA, Uther JB. Curative surgery for atrioventriculor junctional [“AV nodal”) reentrant tachycardia. JACC 1985;6:1383-1392. 32. Waldo AL, MacLean WAH, Karp RB, Kouchoukos NT, James TN. En- trainment and interruption of atria1 flutter with atria1 pacing studies in man following open heart surgery. Circulation 1977;56:737-745. 33. Waldo AL, Plumb VJ, Arciniegas JG, MacLean WAH, Cooper TB, Priest MF, James TN. Transient entrainment and interruption of the atrioventricu-

January 15, I& THE AMERICAN JOURNAL OF CARDIOLOGY Volume 61 19A

lor bypass pathway type of paroxysmal atria1 tachycardia Circulation 1983; 67:73-83. 34. Waldo AL, Henthorn RW, Plumb VJ, MacLean WAH. Demonstration of the mechanism of transient entrainment and interruption of ventricular tachycardia with rapid atria1 pacing. JACC 1984;3:422-430. 35: Lehmann MH, Denker S, Mahmud R, Addas A, Akhtar M. Linking: a dynamic electrophysiologic phenomenon in macroreentry circuits. Circula- tion 1985;71:254-265, 36. Josephson ME, Buxton AE, Marchlinski FE, Doherty JU, Cassidy DM, Kienzle MG, Vassallo JA, Miller JM, Almendral J, Grogan W. Sustained ventricular tachycardia in coronary artery disease-evidence for reentrant mechanism. In: Zipes DP, jalife j, eds. Cardiac Electrophysiologic and Ar- rhythmias. Orlando, FL: Gram 8 Stratton, 1985:499-418. 37. Zipes DP. Arbel E. Knope RF, Moe GK. Accelerated cardiac escape rhythms caused by ouabain intoxication. Am f Cardiology 1974;33:248-253. 38. Desantola JR, Marchlinski FE. Response of digoxin-toxic atria1 tachycar-

dia to digoxin-specific fob fragments. JACC 1987;58:1109-1110, 39. Wieland JM, Marchlinski FE. Electrocardiographic response of digoxin- toxic foscicular tachycardia to jab fragments: implications for tachycardia mechanism. PACE 1986;9:727-738. 40. Rosen MR, Fisch C, Hoffman BF, Danilo P, Lovelace DE, Knoebel SB. Can accelerated atiioventricular junctional escape rhythms be explained by de- layed ofterdepofarizations? Am J CardioI 1980;45:1272-1284. 41. Fisch C, Knoebel SB. Accelerated junctional escape: a clinical manifesta- tion of “triggered” automaticity? In: Zipes DP, jolife j, eds. Cardiac Electro- physiology and Arrhythmias. Orlando, FL: Crune 8 Stratton. 1985:469-478. 42. Dangman KH, Hoffman BF. Studies on overdrive stimulation of canine cardiac Purkinje fibers: maximal diastolic potential as a determinant of the response lACC 1983;2:1183-1190. 43. Ruder MA, Davis JC, Eldar M, Abbott JA, Griffin JC, Seger JJ, Scheinman MM. Clinical and electrophysiologic characterization of automatic junctional tachycardia in adults. Circulation 1986;73:930-937