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Heart Rhythm (2004) 1, 94–106

www.heartrhythmjournal.com

RS-PLENARY LECTURE 2003

rom bedside to bench: Entrainment and other stories

lbert L. Waldo

epartment of Medicine, Division of Cardiology, Case Western Reserve University/University Hospitals of Cleveland,
leveland, Ohio.
The concepts of transient entrainment of reentrant rhythms started with studies of overdrive pacingof atrial flutter (AFL) in patients in the immediate period after open heart surgery. Initial studiesdemonstrated the need to achieve a critical pacing rate and a critical duration of pacing at thecritical pacing rate to interrupt AFL. Further pacing studies of AFL, ventricular tachycardia,atrioventricular (AV) reentrant tachycardia, AV nodal reentrant tachycardia, and atrial tachycardiarefined the understanding of what occurs during overdrive pacing of reentrant tachycardias, andpermitted a mechanistic understanding of transient entrainment as continuous resetting of areentrant tachycardia to a pacing rate that is faster than the rate of the tachycardia, but which failsto interrupt it. The demonstration of transient entrainment of a tachycardia provides a reliableclinical tool to establish the presence of a reentrant rhythm. Moreover, the principles of entrain-ment have also been applied clinically to assist in effective application of antitachycardia pacingand catheter ablation techniques.© 2004 Heart Rhythm Society. All rights reserved.

KEYWORDSReentry;Entrainment;Tachycardias;Rapid pacing

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ntrainment begins with atrial flutter (AFL) and a bed-ide story. When we started these studies, it wasn’t be-ause we knew there was something called entrainment.o, it is important to provide some background. In thearly 1970s, AFL was certainly a long- and well-recog-ized rhythm, but its mechanism was not very well un-erstood. There were two schools, one that thought it wasue to a single focus firing rapidly, and one that thoughtt was due to a reentrant mechanism.1 And at that time,here appeared a series of articles in which investigatorseported attempts to interrupt AFL using rapid atrialacing techniques, introduction of premature atrial beats,

Supported in part by Grants RO1 HL38408 and RO1 HL074189 fromhe National Institutes of Health, National Heart, Lung, and Blood Institute,ethesda, Maryland.

Address reprint requests and correspondence to: Albert L. Waldo,.D., Division of Cardiology, MS LKS 5038, University Hospitals ofleveland, 11100 Euclid Avenue, Cleveland, OH 44106.

E-mail address: [email protected].

547-5271/$ -see front matter © 2004 Heart Rhythm Society. All rights reservedoi:10.1016/j.hrthm.2004.02.002

r both.2 None of these studies were systematic, and theesults were quite variable, i.e., some reported someuccess, and some reported failure.2 In fact, it was ques-ioned whether one could reliably treat AFL with cardiacacing at all. Also, the then-new concept of triggeredhythms was evolving1 and played a role in the story.his was because for a very long time it was thought that

f one could initiate or terminate a tachyarrhythmia withardiac pacing, it meant the tachyarrhythmia was due toeentry.1,3 However, when studies began to teach usbout triggered rhythms, it became apparent that theylso could be initiated or terminated with cardiac pacingechniques.1 Thus, we no longer could use pacing initi-tion or termination of a rhythm as the sine qua non fordentifying whether it was due to reentry. So, this was theerspective when we confronted the management of AFLn patients following open heart surgery.

One day in the fall of 1972, as Dr. William MacLean,hen a postdoctoral fellow in cardiology at The Universityf Alabama at Birmingham (UAB) Medical Center, and I

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ere making rounds, Dr. T. Joseph Reeves, Professor andhairman of the Department of Medicine and a superbardiologist, was about to perform DC cardioversion ofFL in a post–open heart surgical patient. A pair of tem-orary atrial epicardial wire electrodes had been placed athe time of surgery, and Dr. Reeves, aware of recent reportsndicating that AFL could be interrupted by rapid atrialacing, asked us to try to pace the patient’s atria to converthe AFL to sinus rhythm. We decided to give it a try. Theeason we could try was because of the Medtronic SP349A triple pulse generator. And this is also a nice storyrom a different era, but one central to the story of entrain-ent. The SP 1349A was a small, portable, easily hand-

arried device that we were able to use at the bedside. Thisacemaker, built by Medtronic with independent input fromr. S. Serge Barold and me, permitted us to pace very

apidly at precise rates with stimuli of up to 50 mA.2

ithout this device, it would have been far more difficult too this work.

Using overdrive pacing at rates chosen rather arbitrarily,ut faster than the intrinsic rate of the AFL, we tried toerminate it and restore sinus rhythm but couldn’t. Becausef the large volume of patients undergoing open heart sur-ery at UAB and because of the significant incidence ofostoperative AFL, we subsequently had many opportuni-ies to try again. After rereading the several articles thateported attempts to interrupt AFL with pacing, we realizedhat no systematic studies had been performed, that someeported modest success, and that some reported abjectailure. So, we started to do the atrial pacing systematicallysing the SP 1349A pacemaker and the temporary epicar-ial electrodes placed in the high right atrium near the sinusode at the time of the surgery.

igure 1 ECG lead II recorded from a patient with AFL (atrialL � 264 ms) (A) and at the end of 30 s of rapid atrial pacing fromhigh right atrial site at CLs of 254 ms (B), 242 ms (C), and 232s (D). The atrial flutter was transiently entrained at each pacingL. See text for discussion. Time lines are at 1-s intervals. Mod-

fied from reference #2.

acing studies of AFL

e soon found that to use overdrive pacing to interruptFL, pacing had to be performed at a critically rapid rate. If

he overdrive pacing rate was not rapid enough, pacing onlyncreased the AFL to the pacing rate, but with abrupt ter-ination of pacing or slowing of the pacing rate below the

ntrinsic AFL rate, the AFL was still present (Figure 1).2

hen the atria were paced at a sufficiently rapid rate, theFL was finally interrupted (Figure 2), but we didn’t un-erstand why. Moreover, not only was a critical pacing rateequired, but a critical duration of pacing at the criticalacing rate was also required (Figure 2).2 The observationsrom Figure 2 were seminal, because with this case weecognized that when pacing from a site high in the righttrium, interruption of classical AFL was associated withhe appearance of a positive P wave in ECG leads II, III, andVF. This, we recognized, was a marker that the AFL hadeen interrupted, because a positive atrial complex in thoseeads was what was expected when overdriving sinushythm from a high right atrial pacing site. But the expla-ation for the sudden change in morphology of the atrialomplexes in the ECG (Figure 2) was initially not apparent.oreover, this sudden change in atrial complex morphol-

gy in the ECG was associated with a decrease in activationime from the high right atrial pacing site to the posterior-nferior left atrial electrode recording site. The latter wasocumented by a dramatic shortening (mean 100 ms) ofctivation time from the high right atrial pacing site to theosterior-inferior left atrial recording site.2 But this, too,as not yet understood except as a marker of successfulFL interruption.

igure 2 (A): ECG lead II recorded from the same patient asigure 1 during high right atrial pacing from the same site at a CLf 224 ms. With the 7th beat in this tracing, and after 22 s of atrialacing at a constant rate, the atrial complexes suddenly becameositive. (B): ECG lead II recorded from the same patient. Withbrupt termination of pacing, sinus rhythm occurs. (C): Continuedinus rhythm. See text for discussion. Asterisk � same beat.odified from reference #2.

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96 Heart Rhythm, Vol 1, No 1, May 2004

We performed a series of atrial overdrive pacing studiesf AFL in patients and reported it.2 In that paper, we coinedhe term “transient entrainment of a tachycardia” and de-ned it as an increase in the rate of a tachycardia to a fasteracing rate, with resumption of the tachycardia either uponbrupt cessation of pacing or slowing of the pacing rateelow the intrinsic rate of the tachycardia. This was aescriptive definition because we did not yet understandntrainment fully.

tudies of ventricular tachycardia (VT)

e then started to examine overdrive pacing of other tachy-rrhythmias. The stories continue with VT. We now dem-nstrated that when pacing the ventricles at a rate faster thanhe tachycardia rate, a critical pacing rate was required tonterrupt the tachycardia.4 What was new was the clearecognition of progressive fusion of the QRS complexes inhe ECG during pacing at two or more constant rates fasterhan the rate of the tachycardia, in which each rate failed tonterrupt the tachycardia (Figure 3). We put these dataogether and submitted a paper describing transient entrain-ent of VT but were turned down consecutively by three

eer-reviewed journals. On appeal to the third journal, itas finally published4 but not without an editorial entitled

Entrainment of ventricular tachycardia: all aboard or thend of the line.” The editorial was basically supportive butuite tentative.5

nderstanding entrainment–The breakthroughase and development of the first threentrainment criteria

he critical insight into entrainment that led to its under-tanding finally resulted from analysis of a single case ofntrainment and interruption of VT, again performed at the

igure 3 ECG lead II recorded from a patient with VT at a ratef 150 bpm. Top trace: termination of ventricular pacing (dot) at aate of 160 bpm, with prompt return of VT; middle trace: termi-ation of pacing (dot) at a rate of 175 bpm, with prompt return ofT; bottom trace: termination of pacing at a rate of 190 bpm, with

uccessful interruption of the VT. See text for discussion. Modifiedrom reference #4.

edside with the SP1349A temporary pacemaker.6 Andhat we finally figured out during transient entrainment and

nterruption of reentrant VT turned out to be true for everyingle ordered reentrant tachyarrhythmia (AFL, VT, atrio-entricular reentry tachycardia [AVRT], AV nodal reentryachycardia, and atrial tachycardia) we have studied.1 More-ver, the phenomena observed during transient entrainmentnd interruption of tachycardias identified the mechanism aseentrant.1

The breakthrough case was one of postoperative VT with:1 retrograde atrial activation. That gave us the idea thaterhaps we could pace the atria and interrupt the VT, espe-ially because this VT was relatively slow (141 bpm) andell tolerated. Figure 4 shows the first of a series of dia-rams using a figure-of-eight model of reentry with a centralsthmus to represent the reentrant VT circuit. At the time,e thought that the isthmus represented an area of slow

onduction. But as we now know from the work of Wit etl,1 the area of slow conduction in this model is probablyhere block is thought to occur on either side of the isth-us. For purposes of historical accuracy, we shall again use

he figure-of-eight reentry circuit to illustrate what wehought was occurring during entrainment and interruptionf the VT.

In Figure 4, the top left panel illustrates the VT waveronts traveling around the reentrant circuit. With the onsetf atrial pacing (Figure 4, top middle panel) at 150 bpm, aate faster than the VT, the ventricular wave front from theacing impulse is able to enter the excitable gap of theeentrant circuit, where it travels both antidromically andrthodromically. Antidromically, it collides with the ortho-romic wave front of the previous beat, creating a fusioneat in the ECG. Orthodromically, it enters the reentrantircuit early, so that it captures the reentrant circuit andesets it to the pacing rate. Because this orthodromic waveront isn’t blocked, it travels around the reentrant circuitntil it collides with the antidromic wave front of the nextaced beat (Figure 4, top right panel). Thus, during pacing,here is constant fusion of the QRS complex morphology inhe ECG, as the ventricles are activated simultaneously byave fronts from two different paced beats, and there is

ontinuous resetting of the tachycardia to the pacing rate byhe orthodromic wave from each pacing impulse. This, inact, is the mechanistic definition of transient entrainment:ransient entrainment of a tachycardia occurs during pacingt a rate faster than the tachycardia rate when each ortho-romic wave front from the pacing impulse resets the tachy-ardia to the pacing rate, and each antidromic wave frontrom the pacing impulse either collides with the ortho-romic wave front of the previous beat or is otherwiselocked.

The actual ECG and ventricular electrogram (VEG) re-ordings (atrial pacing at 150 bpm, with 1:1 capture of theentricles) are shown in the bottom panel of Figure 4. Notehat during pacing, the QRS complexes have changed inorphology and are narrower (120 ms) compared to those

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97Waldo Entrainment

uring the spontaneous VT, but the VEG morphology washe same during pacing as during the spontaneous VT,ndicating that activation at this recording site was the samen both instances.

The top panel of Figure 5 diagrammatically illustrateshat happened when we stopped pacing. The top left panel

hows the last paced beat, and, as expected, its antidromicave front collides with the orthodromic wave front of therevious beat, creating a fusion beat in the ECG (the ven-ricles are activated simultaneously by wave fronts from two

igure 4 Top panel: Diagrammatic representation of transient eniagrams, arrows indicate direction of activation, box represents ansic], dashed line indicates the excitable gap in the reentry circuit,arge arrow (middle and right panels) indicates wave front from there it is conducted orthodromically (ortho) and antidromicallyodel) during VT at a rate of 141 bpm. x � orthodromic wave fro

acing impulse (x � 1) during atrial pacing at a rate of 150 bpmrthodromic wave fronts of the previous spontaneous beat (x), reowever, the orthodromic wave front from the pacing impulse co

ntroduction of the second pacing impulse (x � 2) during atrial prthodromic wave fronts (x � 1) of the previous paced beat, againgain, the orthodromic wave front from the pacing impulse (x � 2acing, the VEG site is always activated by an orthodromic waveith a bipolar atrial electrogram (AEG) and a unipolar ventricular

nd Figure 5, the circled number indicates the duration (ms) of eaimultaneously with the atrial pacing (A Pace) stimulus (S) artifactt 150 bpom (400 ms CL). Time lines are at 1-second intervals. S

ifferent beats). The orthodromic wave front of the lastaced beat again resets the tachycardia to the pacing rate,ut this time, this orthodromic wave front, which travelsround the reentrant circuit at the pacing cycle length, isnopposed because there is no subsequent pacing impulse.herefore, this last captured beat is entrained, but there is no

usion in the ECG. The bottom panel of Figure 5 shows thectual ECG and EG recordings. The last pacing impulseaptured the ventricles at the 400 ms pacing cycle lengthCL), but while the last captured ventricular beat was en-

ent, in this case, of VT during atrial pacing. In this and subsequents in the reentrant circuit, serpentine line indicates slow conductionpresents a right ventricular electrogram (VEG) recording site, anding impulse entering the excitable gap of the VT reentry circuit,. Top left panel: Diagram of the reentry circuit (figure-of-eightthe reentrant rhythm. Top middle panel: Introduction of the firstg the VT. The antidromic wave fronts (x � 1) collide with thein a fusion ventricular beat, which, in effect, interrupts the VT.the tachycardia, resetting it to the pacing rate. Top right panel:t 150 bpm. The antidromic wave fronts (x � 2) collide with the

g ventricular fusion, which, again, in effect, interrupts the VT. Butinues the VT, resetting it to the pacing rate. During the period ofottom left panel: ECG leads I and V1 recorded simultaneously

gram (VEG) during VT at a rate of 141 bpm (425 ms CL). In thisS complex. Bottom right panel: ECG leads I and V1, recordednd the unipolar ventricular electrogram (VEG) during atrial pacingt for discussion. Modified after reference #6.

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rained (asterisk), it was not fused. In fact, because therthodromic wave front from the last pacing impulse wasnopposed by a subsequent antidromic pacing wave front,his beat had the QRS complex morphology of the sponta-eous VT. From these observations came the first entrain-ent criterion: during a tachycardia, when pacing at a con-

igure 5 Diagrammatic representation and tracings of the terminatieft panel: The wave front from the last pacing impulse (rate 150 bprthodromically and antidromically. The antidromic wave fronts, xn(a

rthodromic wave front xn(o) from the last pacing impulse continurthodromic wave fronts from the last pacing impulse are now unompulse, so that no fusion of ventricular activation occurs despite thachycardia (dashed lines), which then resumes at its previous spontanhe atrial pacing (A Pace) stimulus (S) artifact (stim) or atrial electrogrf atrial pacing at a rate of 150 bpm (400 ms CL). In this and subseqhe last entrained beat, the arrow from the stimulus in the VEG points

s); the dashed arrow in lead I represents the last antidromic wave fr

n(o) from the last pacing impulse. See text for discussion. Modified

tant rate that is faster than the rate of tachycardia and whichails to interrupt it, there is the demonstration of constantusion beats in the ECG except for the last captured beat,hich is not fused.1

Then with atrial pacing at 155 bpm, the same thingappened. The VT circuit was captured, the morphology of

rial pacing at 150 bpm, illustrating the first entrainment criterion. Toprs the excitable gap of the VT reentry circuit, where it is conductede with the orthodromic wave fronts xn-1, causing a fusion beat. Thetachycardia, resetting it to the pacing rate. Top right panel: Theby antidromic wave fronts because there is no subsequent pacing

nce of transient entrainment. This last entrained beat continues thete. Bottom panel: ECG leads I and V1 recorded simultaneously with

G), and the unipolar ventricular electrogram (VEG) at the terminationgures, the open circle denotes the last stimulus, the asterisk denotesresulting VEG (with the stimulus-to-VEG interval being indicated in

n(a); and the solid arrow represents the last orthodromic wave fronts,ference #6.

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he QRS complexes changed even more, and narrowed to 91s in duration (Figure 6). Also, as before, the VEG mor-

hology was unchanged from that during spontaneous VT.nd as before, the last pacing impulse captured the ventri-

les at the pacing CL, now 387 ms, but the morphology ofhe last captured beat was not fused. Because the pacing CLas shorter, the antidromic wave front from each pacing

mpulse entered the excitable gap earlier, resulting in colli-ion with the orthodromic wave front of the previous beat atdifferent place (Figure 6). This created constant fusionRS complexes in the ECG which were different than seenhen pacing at 150 bpm (Figures 4 and 5). And then whenacing the atria at 160 bpm, there was a still different QRSomplex morphology, and the QRS complex was now only0 ms in duration (Figure 6), but the ventricular electrodeecording site was still activated from the same directionuring pacing as during the spontaneous tachycardia, andhe last captured beat was not fused. Because this pacing CLas shorter (375 ms), the antidromic wave front of eachacing impulse was able to penetrate still further into the

igure 6 Illustration of the second entrainment criterion. Topllustrated in Figure 4 during pacing at 150 bpm, 155 bpm, and 1mpulse, xn(a), collide with the orthodromic wave front of the prevach pacing impulse, xn(o), transiently entrains the VT by resettinghe pacing rate increases, the antidromic wave fronts from each paegree. Therefore, although ventricular fusion occurs in each instan the ECGs (see bottom panel). Bottom panel: ECG leads I and V1

trial pacing which transiently entrains the VT at 150 bpm (B), 155odified after reference #6.

eentrant circuit (Figure 6), explaining the yet again differ-nt QRS complex morphology of the fusion beats in theCG leads. The different degree of fusion in the ECG leadst each pacing rate, which entrains but fails to interrupt theachycardia, is called progressive fusion (Figure 6). Fromhese observations came the second entrainment criterion:uring a tachycardia, when pacing at two or more constantates that are faster than the rate of the tachycardia buthich fail to interrupt it, there is the demonstration of

onstant fusion beats in the ECG at each rate, but differentegrees of constant fusion at each rate.1

Then with atrial pacing at a rate of 165 bpm (CL of 364s), still with 1:1 conduction to the ventricles (Figure 7, top

anel), initially there is further progressive fusion of theRS complexes in the ECGs. Then, denoted by the aster-

sks, there was an abrupt change in morphology of both theecorded QRS complexes in the ECG leads and the VEGs.mmediately before the change in morphology of the QRSomplexes and of the VEG, the stimulus-to-VEG intervalas 640 ms. Then, there was localized conduction block to

Diagrammatic representation of transient entrainment of the VT. In each example, the antidromic wave fronts from each pacingat, xn-1. However, in each case, the orthodromic wave front from

the pacing rate. Because the pacing CL progressively shortens aspulse at each faster rate penetrate the reentry circuit to a greater

e degree of fusion is different. This results in progressive fusioned simultaneously during VT at a rate of 141 bpm (A), and during), and 160 bpm (D). S � stimulus artifact. See text for discussion.

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he VEG recording site for one beat (i.e., the impulse fromhe next stimulus never activated this recording site), afterhich, the impulse from the next stimulus was conducted to

hat site with a stimulus-to-VEG interval of only 305 ms.

igure 7 Illustration of the third entrainment criterion. Top pantimulus (s) artifact (stim), and the unipolar ventricular electrograhe VT. The asterisks denote an abrupt change in configuration ohe change in configuration of the QRS complexes and VEG, the s

EG recording site, this interval becomes 305 ms. Note also that thhe beat-to-beat CL localized to the VEG recording site (from 364ottom panel is a diagrammatic representation of events recordedottom left panel: The wave front from the pacing impulse enntidromically, x � 1(a), and orthodromically, x � 1(o). The antidroeat (x), causing a fusion beat. Note that this collision is at a siterthodromic wave front is also blocked during the same cycle. No

1(o), although activated by the orthodromic wave front (x) of text pacing impulse at the same 165 bpm rate (x � 2) now activx � 1) paced beat, the sequence of ventricular activation during xhe sites which had just demonstrated localized conduction blockirection and with a shorter conduction time. This is because theree text for discussion. Modified from reference #6.

his localized conduction block was associated with anncrease in the beat-to-beat CL at the VEG recording siterom 364 ms to 425 ms and then back to 364 ms. There waso such increase in the QRS complex CLs. In the ECG lead

G leads I and V1 recorded simultaneously with the atrial pacing

G) during atrial pacing at 165 bpm (364 ms CL) which interruptscorded QRS complexes in both ECG leads and the VEG. Before-to-VEG interval is 640 ms. Then, after the localized block to the

alized conduction block is associated with a one-cycle increase inms, and then back again to 364 ms). S � stimulus artifact. The

panel during the interruption of the VT with pacing at 165 bpm.excitable gap of the VT reentry circuit, where it is conducted

ve fronts collide with the orthodromic wave fronts of the previousifferent than that illustrated in Figure 6. However, this time, thesites immediately orthodromically distal to the site of block of xious beat, are not activated by x � 1. Bottom right panel: The

e ventricles. But because the VT was interrupted by the previousas expected during atrial overdrive pacing of sinus rhythm. Thusbeat, including the VEG site, are now activated from a different

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tracing, the dashed arrows represent the antidromic waveronts, and the associated solid arrows represent the ortho-romic wave fronts from the fifth and sixth pacing impulseshown in the figure. After the block of both the antidromicnd orthodromic wave fronts of the sixth pacing impulse inhe reentrant circuit of the VT, the ventricles were activatedy the seventh pacing impulse as expected during overdrivetrial pacing of a sinus rhythm because the VT has beennterrupted. This, of course, explains the change in mor-hology of the QRS complexes and the VEGs. Finally, hadhe pacing been terminated prior to achieving block of bothhe antidromic and orthodromic wave fronts of the sameacing impulse during the same beat, the tachycardia wouldot have been interrupted, emphasizing the critical durationf pacing at the critical pacing rate required for interruptionf the tachycardia.

Termination of the tachycardia is shown diagrammati-ally (Figure 7, bottom panel). When pacing the atria at 165pm, the antidromic wave front of the pacing impulse col-ided, as usual, with the orthodromic wave front of therevious beat. But now the orthodromic wave front of thatame pacing impulse also blocked, so that an area of theentricles was never activated by this paced beat. This isocalized conduction block. With block of both the anti-romic and orthodromic wave fronts of the atrial pacingmpulse during the same beat, the tachycardia was inter-upted, and the functionally determined components of theeentrant circuit disappeared. Thus, with the next atrialacing impulse at the same 165-bpm rate, the site that just

igure 8 ECG lead II also shown in Figure 2, but now shownecorded simultaneously with the stimulus artifact (stim) fromhe high right atrial pacing site. Arrows drawn from eachtimulus artifact represent the antidromic (a) and orthodromico) wave fronts from each pacing impulse in association withach atrial complex in the ECG. Note that the appearance of theositive atrial complex in the ECG is associated with block ofoth the antidromic and orthodromic wave fronts of the sameacing impulse during the same cycle. The antidromic waveront blocks because it collides with the orthodromic wave frontf the previous wave front, as usual. When the orthodromicave front of the same beat blocks during the same cycle, theFL is interrupted, and continued atrial pacing activates the

tria from the high right atrial pacing site as expected duringinus rhythm. Modified after reference #2.

emonstrated localized conduction block gets activatedrom a different direction and with a shorter conductionime. From this came the third entrainment criterion: during

tachycardia, when pacing at a constant rate that is fasterhan the rate of tachycardia and which interrupts it, there ishe demonstration of localized conduction block to a site orites for one beat followed by activation of that site or thoseites by the next paced beat from a different direction andith a shorter conduction time.1

Now we can understand what happened in Figure 2 in thativotal case of AFL. Recall that after the 22 s of high righttrial pacing at a constant rate of 373 bpm, suddenly there washe appearance of positive P waves in ECG lead II. Now wenow that during entrainment, the antidromic wave front ofach atrial pacing impulse collided with the orthodromic waveront of the previous beat, and each orthodromic wave fronteset the tachycardia to the pacing rate. But when the anti-romic and orthodromic wave fronts of the same pacing im-ulse blocked during the same beat, the tachycardia was inter-upted. Thus, the next pacing impulse captured the atria as ifverdriving sinus rhythm. Since pacing was being performedrom the high right atrium, a positive P wave appeared in ECGead II (Figure 8). So, we finally understood what happeneduring entrainment and interruption of classical AFL whenacing from the high right atrium.

he fourth entrainment criterion

ith these studies, we recognized that it is sometimes hardo see or demonstrate some of these entrainment criteria,articularly fusion in the ECG, when pacing the atria duringFL or a reentrant atrial tachycardia. From that evolved the

ourth entrainment criterion: During a tachycardia, whenacing at two constant rates that are faster than the rate ofachycardia but which fail to interrupt it, there is the dem-nstration of a change in conduction time to and EG mor-hology at an electrode recording site.1,7 This is the EGquivalent of the second criterion.

Figure 9 well illustrates the fourth entrainment criterionn a patient during atrial pacing from the high right atriumHRA) during an AVRT (CL 339 ms). Shown in both panelss ECG lead II recorded simultaneously with EGs from theroximal pair of electrodes of a catheter placed in the HRAnd the coronary sinus (CS) during termination of pacing atLs of 308 ms (Figure 9, panel A) and 292 ms (Figure 9,anel B). In the recordings from the CS, the arrows fromach stimulus artifact (S) indicate the AEGs (a) that resultedrom that stimulus. Note that the AEGs at the CS site inanel A were identical to that during the spontaneoushythm, and that conduction time during pacing was long390 ms). However, with pacing at a shorter CL (292 ms) inanel B, the AEG morphology changed at the CS site duringntrainment, indicating that this site was now activated fromdifferent direction and a shorter conduction time (90 ms).ote also that the tachycardia was not interrupted by pacing

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igure 9 Illustration of the fourth criterion of transient entrainment during atrial pacing from the high right atrium (HRA) during antrioventricular reentrant tachycardia (AVRT), CL 339 ms. In the upper part of both panels A and B, ECG lead II is recorded simultaneouslyith bipolar EGs from the proximal pair (p) of catheter electrodes in the HRA and the coronary sinus (CS) during termination of pacing

t a CL of 308 ms (panel A) and 292 ms (panel B). In the CS recordings, the arrows from each stimulus (s) indicate the atrial complexesa) that result from that stimulus. V � ventricular complex. The last arrow in each panel goes to the last transiently entrained beat. S �timulus artifact. The bottom diagrams in each panel represent the recorded events during pacing at each CL. The left panel of each diagramndicates the pacing impulse (x � 1) from the HRA entering into the reentry circuit, whereupon it is conducted antidromically andrthodromically. The antidromic wave front collides in the atria with the orthodromic wave front (x) of the previous beat in panel A butn the AV bypass pathway in panel B. However, in each case, the orthodromic wave front, which is not blocked during that beat, resets theachycardia to the pacing rate, continuing the tachycardia. Thus, with the last paced beat, the unopposed orthodromic wave front from theast paced beat continues the tachycardia. In panel B, note that with resumption of the AVRT, the CS will again be activated orthodromicallyit had been activated antidromically during pacing at 292 ms CL). Serpentine line represents slow conduction in the AV node. See text foriscussion. Modified after reference #7.

igure 10 Diagrammatic representation of one form of concealed entrainment of VT by pacing from an isthmus in a reentry circuit. Leftanel shows the last paced beat (xn) during concealed entrainment. The square wave indicates the pacing site. xn-1 � orthodromic waveront of the next-to-last paced beat. The antidromic wave front from the last pacing impulse blocks (unidirectional block) within or very closeo the isthmus. The orthodromic wave front from the last pacing impulse activates the ventricles virtually identically as during thepontaneous VT, so that there is no fusion QRS complex morphology in the ECG. Middle and right panels: Following the last paced beatx ), the VT resumes at its previous rate. See text for discussion.
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t either rate. This fulfilled the fourth criterion for demon-tration of transient entrainment. As diagrammatically illus-rated in the bottom half of Figure 9, panels A and B, the CSite was activated orthodromically during pacing at a CL of08 ms but antidromically during pacing at a CL of 292 ms.ctually, in Figure 9, panel A, the disappearance of aositive P wave in the ECG with the last captured beat thatas entrained but not fused, is apparent, also fulfilling therst entrainment criterion. Finally, note also in Figure 9,anel B that with the last paced beat, the CS site was firstctivated antidromically and then orthodromically by theame beat because the orthodromic wave front from the lastaced beat is not blocked.

igure 11 Diagrammatic representation of another form of conce65 bpm from a site immediately distal to an area of slow conducf the same VT seen in Figures 4–7. Dashed lines represent the excmpulse. X � circulating reentrant wave fronts of the VT. Top midmpulse entering the reentrant circuit, where it is conducted ortholocks in an area of slow conduction (unidirectional block). The oranel: The orthodromic wave fronts from the last pacing impulse coate. Bottom left 2 panels: Diagrammatic representations of concepm from the same site shown in the top panel. Note the absencend antidromic wave fronts, respectively, from the pacing impulse.f VT pacing at 165 bpm from the same pacing site as shown in tt a rate of 165 bpm enters into the VT reentrant circuit. The antidron the same place as during pacing at 150, 155, and 160 bpm. Teentrant circuit as before, but now it is also blocked, presumably inrom the ECG or from standard electrode catheter recording sites. Wacing impulse blocks as just described. Only then, with no furtheor discussion. Modified after reference #10.

oncealed entrainment

tachycardia may be transiently entrained and even inter-upted without being able to demonstrate any of the entrain-ent criteria, i.e., there may be concealed entrainment.1,8–11

hen this occurs, to prove the presence of entrainment,acing must be performed from a site demonstrating man-fest entrainment. There are two types of concealed entrain-ent described.This next diagram (Figure 10) illustrates and explains

ne form of concealed entrainment in a figure-of-eight re-ntrant VT circuit. During pacing from an isthmus in theircuit, with pacing at a rate a little faster than the sponta-

ntrainment during ventricular pacing at rates of 150, 155, 160, andthe reentry circuit. Top left panel: Diagrammatic representationap. Xn-1 � the orthodromic wave fronts of the next-to-last pacing

nel: The large arrow represents the wave front from the last pacingally, Xn(o), and antidromically, Xn(a). The antidromic wave front

ic wave fronts reset the tachycardia to the pacing rate. Top rightaround the reentrant circuit, so that the VT resumes at its previous

ntrainment during ventricular pacing at rates of 155 bpm and 160gressive fusion. X � 1(o) and X � 1(a) indicate the orthodromic

right 2 panels: Diagrammatic representation of the interruptioner and 2 left panels. The wave front from the last pacing impulseave front of the pacing impulse is again blocked (unidirectionally)odromic wave front from the pacing impulse travels around theea of slow conduction. However, this cannot be appreciated eithere termination of pacing, the orthodromic wave front from the lastg, can it be appreciated that the VT has been interrupted. See text

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eous rate, the orthodromic wave front of the pacing im-ulse captures the circuit and resets it, but the antidromicave front blocks it. Some suggest the latter blocks because

t collides with the previous orthodromic wave front cominground the reentrant circuit. We suggest another possibility,hat the antidromic wave front blocks in the isthmus, per-aps in an area of slow conduction, so that the antidromicave front never really exits. In any event, at best, there isinimal antidromic penetration. Therefore, a fusion mor-

hology is not appreciated in the ECG because virtually allites are activated the same way during pacing as during theachycardia except for a very small area activated anti-romically. Because the tachycardia is entrained but there iso evidence of that in ECG, the entrainment is concealed.ven with interruption of the tachycardia, there is no pos-ible demonstration of any of the entrainment criteria. Whatappens with the last paced beat is that the orthodromicave front from the pacing impulse goes around the reen-

rant circuit, and the tachycardia resumes (Figure 10). Un-erstanding this form of concealed entrainment has becomeery useful, particularly during ablation of the so-calledFL isthmus and during ablation of VTs with an isthmus, in

oncert with criteria of Stevenson et al,12 which use theostpacing interval to demonstrate the participation of sitesn the reentrant circuit.

igure 12 Demonstration of concealed entrainment of AFL. ECerminalis (ST) and Bachmann’s bundle (BB) at the termination orom the postero-inferior left atrium in a patient with AFL (rateermination at each rate fails to show any evident transient entrainmn fact, only when pacing was stopped was it realized that AFL hauring atrial pacing. Time lines are at 1-s intervals. See text for dransient entrainment and related phenomena. In: Zipes DP, JalifeB Saunders Co; 1990. p. 530–537.

There is another form of concealed entrainment that weescribed,8,10 but which is not widely appreciated. It occurshen pacing from a site orthodromically distal to an area of

low conduction. Using as illustration the same VT shownn Figures 4 through 7, if the ventricles are paced at rates of50, 155, and 160 bpm from a site immediately distal to anrea of slow conduction in the reentry circuit (Figure 11),he tachycardia will be entrained because the pacing im-ulse will enter the excitable gap and reset the tachycardiao the pacing rate. However, despite the fact that the tachy-ardia is entrained and subsequently interrupted when pac-ng at 165 bpm, none of the criteria of transient entrainmentill be demonstrable. When pacing orthodromically distal

o an area of slow conduction at 150 bpm (Figure 11, topanel), each pacing impulse enters the excitable gap of theeentry circuit. The antidromic wave front encounters blockeither unidirectional or, less likely we suggest, due toollision with the orthodromic wave front of the previouseat) in the area of slow conduction. The orthodromic waveront of each pacing impulse resets the tachycardia to theacing rate. When pacing is terminated, the orthodromicave front of the last paced beat continues the tachycardia.ince the last captured beat has the same morphology as that

hroughout the period of pacing,13 the first criterion ofransient entrainment cannot be met.

III is recorded simultaneously with bipolar AEGs from the sulcusof rapid atrial pacing (352 bpm–left panel; 365 bpm–right panel)

bpm). Comparison of events during rapid atrial pacing and itsiteria, even despite interruption of the AFL by pacing at 365 bpm.

interrupted. S � stimulus artifact. Asterisk � last captured beation. From: Waldo AL, Carlson MD, Hethorn RW. Atrial flutter:. Cardiac Electrophysiology: From Cell to Bedside. Philadelphia:

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With pacing at 155 or 160 bpm (Figure 11, bottomanel), because the pacing CL is shorter than pacing at 150pm, the wave front from each pacing impulse enters theeentry circuit earlier, but block of the antidromic waveront still occurs at the same place. The orthodromic waveront continues to activate the ventricles as during pacing at50 bpm. Thus, the QRS complex during pacing at theseaster rates does not change, and progressive fusion, theecond entrainment criterion, will not be present. Therefore,he fourth criterion also will not be present. Finally, whenacing at a sufficiently rapid rate (165 bpm), interruption ofhe VT occurs because now the orthodromic wave frontlocks independently, presumably in the area of slow con-uction (Figure 11, bottom right panel), along with block ofhe antidromic wave front of the same paced beat. However,he only way to know that interruption of the tachycardiaas occurred is to stop pacing because the third criterion ofransient entrainment is not demonstrable. In sum, pacingrom a site orthodromically distal to an area of slow con-uction may not permit the demonstration of manifest en-rainment.

Figure 12 is a representative example of this type ofoncealed entrainment in a case of AFL during pacing fromhe CS. The left panel demonstrates the termination ofacing at a rate (352 bpm) faster than the rate of the AFL.lthough the atria are clearly captured at the pacing rate,ote the absence of anything to distinguish the last capturedtrial beat from the other captured atrial beats or even fromhe atrial complexes seen during AFL. With cessation ofacing, the AFL resumes at its previous rate. The right panelemonstrates pacing at 365 bpm. Despite pacing at a fasterate, there is again no change in the morphology of the atrialomplexes compared with that during pacing at the slowerate. However, this time, with cessation of pacing, the AFLas been interrupted. There is no evidence during pacinghat the AFL had been interrupted. In fact, the only way tonow that the AFL has been interrupted is to stop pacing.

onclusions

learly, we have learned quite a lot about entrainment overhe years. We have learned that transient entrainment of aeentrant tachycardia occurs during pacing at a rate fasterhan the tachycardia rate when each orthodromic wave frontrom the pacing impulse resets the tachycardia to the pacingate and each antidromic wave front from the pacing im-ulse either collides with the orthodromic wave front of therevious beat or is otherwise blocked. That holds for everyeentrant rhythm studied, including atrial tachycardia, AFL,V nodal reentrant tachycardia, AVRT, and VT.1 Sinusode reentry has not been studied. Unfortunately, one can-ot always demonstrate the entrainment criteria despiteverdrive pacing of a reentrant rhythm. When that happens,oncealed entrainment occurs.

The ideas and concepts of entrainment, I’m glad to say,ave been carried further by many others. Entrainment still

emains the way we can clinically identify reentranthythms. And it is now used regularly as a clinical tool, notnly to identify the mechanism, but also as an essential aidn antitachycardia pacing and catheter ablation procedures.

cknowledgments

My sincere thanks to the NASPE Annual Scientific Ses-ion Program Committee for inviting me to give this dis-inguished lecture. It is an honor and a special privilege fore for several reasons, not only because I have NASPE iny blood, but also because the theme of this 24th Annualcientific Session, “From bench to bedside and back,” isomething I’ve tried to do throughout my career.

We wish to acknowledge so many colleagues who haveelped us develop the concepts and data on entrainment. Men-ioned here are those with whom we have published studies:

illiam A.H. MacLean, Ken Okumura, Richard W. Henthorn,rian Olshansky, Terry B. Cooper, Vance J. Plumb, Joaquin. Arciniegas, Thomas N. James, Nicholas T. Kouchoukos,obert B. Karp, Paul G. Hess, Marshall F. Priest, Andrew E.pstein, Pedro Brugada, Hein J.J. Wellens, Akihiko Shimizu,kira Nozaki, Yoram Rudy, Dalmo Moreira.

eferences

1. Waldo AL, Wit AL. Mechanism of cardiac arrhythmias and conduc-tion disturbances. In: Fuster V, Alexander RW, O’Rourke RA, RobertsR, King SB, Wellens HJJ, editors. Hurst’s The Heart. 10th ed. NewYork: McGraw-Hill Companies, 2001:751–796.

2. Waldo AL, MacLean WAH, Karp RB, Kouchoukas NT, James TN.Entrainment and interruption of atrial flutter with atrial pacing: Studiesin man following open heart surgery. Circulation 1977;56:737–745.

3. Wellens HJJ. Value and limitations of programmed electrical stimu-lation of the heart in the study and treatment of tachycardias. Circu-lation 1978;57:845–853.

4. MacLean WAH, Plumb VJ, Waldo AL. Transient entrainment andinterruption of ventricular tachycardia. Pace Card Electrophysiol 1981;4:358–366.

5. Fisher JD. Entrainment of ventricular tachycardia: All aboard or theend of the line? Pace Card Electrophysiol 1981;4:467–468.

6. Waldo AL, Henthorn RW, Plumb VJ, MacLean WAH. Demonstrationof the mechanism of transient entrainment and interruption of ventric-ular tachycardia with rapid atrial pacing. J Am Coll Cardiol 1984;3:422–430.

7. Henthorn RW, Okumura K, Olshansky B, Waldo AL. A fourth crite-rion for transient entrainment: The electrogram equivalent of progres-sive fusion. Circulation 1988;77:1003–1012.

8. Okumura K, Henthorn RW, Epstein AE, Plumb VJ, Waldo AL. Fur-ther observations on transient entrainment: Importance of pacing siteand properties of the components of the reentry circuit. Circulation1985;72:1293–1307.

9. Frank R, Tonet JL, Kounde S, Farenq G, Fontaine G. Localization of thearea of slow conduction during ventricular tachycardia. In: Brugada P,Wellens HJJ, editors. Cardiac Arrhythmias: Where To Go From Here?Mt. Kisco, NY: Futura Publishing Co., Inc., 1987:191–208.

0. Waldo AL, Henthorn RW. Use of transient entrainment during ven-tricular tachycardia to localize a critical area in the reentrant circuit forablation. Pace Card Electrophysiol 1989;12:231–244.

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1. Feld GK, Fleck P, Chen P-S, et al. Radiofrequency catheter ablationfor the treatment of human Type I atrial flutter: Identification of acritical zone in the reentrant circuit by endocardial mapping tech-niques. Circulation 1992;86:1233–1240.

2. Stevenson WG, Khan H, Sager P, et al. Identification of reentry circuitsites during catheter mapping and radiofrequency ablation of ventric-

ular tachycardia late after myocardial infarction. Circulation 1993;88:1647–1670.

3. Okumura K, Olshansky B, Henthorn RW, Epstein AE, Plumb VJ,Waldo AL. Demonstration of the presence of slow conduction duringsustained ventricular tachycardia in man. Circulation 1987;75:369–378.

from bedside to bench: entrainment and other stories

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