Induction of Atrioventricular Nodal Reentrant Tachycardia

After Atropine

Report of Five Cases

MASOOD AKHTAR, MD ANTHONY N. DAMATO, MD WILLIAM P. BATSFORD, MD ANTONIO R. CARACTA, MD JEREMY N. RUSKIN, MD GERALD M. WEISFOGEL, MD SUN H. LAU, MD

Staten Island, New York

From the Cardiopulmonary Laboratory, U. S. Public Health Service Hospital, Staten Island, N. Y. This work was supported in part by the Bu- reau of Medical Services, U. S. Public Health Service Project Py 75-1 and National Heart and Lung institute Project HE 12536-04. Manuscript accepted December 18, 1974.

Address for reprints: Masood Akhtar, MD, Cardiopulmonary Laboratory, U. S. Public Health Service Hospital, Staten Island. N. Y. 10304.

After intravenous adminlstration of 0.5 mg of atropine sustained atrio- ventricular (A-V) nodal reentrant tachycardia could be produced in flve patients who had no prior historical or electrocardiographic evidence of supraventricular tachycardia. During the control period single atrial echo beats could be demonstrated in four of the five patients, but no Instance of sustained tachycardla occurred. Atroplne, known to en- hance A-V nodal conduction, allowed achievement of longer A-H inter- vals (Case 1) and provided the necessary balance of conductlon and refractoriness within the A-V nodal reentrant pathways (Cases 1 to 5) to sustain A-V nodal reentry in these patlents.

It has repeatedly been observed that a critical degree of atrioventric- ular (A-V) nodal conduction delay is required for the demonstration of manifest A-V nodal reentry and the initiation of A-V nodal reen- trant supraventricular tachycardia. l-lo This critical degree of A-V nodal delay can be achieved either with appropriately timed prema- ture atria1 beats occurring during the relative refractory period of the A-V node or with rapid atria1 pacing.g Less well appreciated is the fact that sustained A-V nodal reentry requires a critical balance be- tween conduction and refractoriness within the reciprocating limbs of a reentrant circuit.

During the conduct of previous studies”J2 designed to evaluate the effects of atropine on A-V conduction and refractoriness, we en- countered five patients who had only single or no atria1 echo beats due to A-V nodal reentry during the control period but who had sus- tained A-V nodal reentrant tachycardia after administration of small doses of atropine (0.5 mg intravenously). We postulate that atropine, known to enhance A-V nodal conduction, permitted the necessary balance of conduction and refractoriness to allow sustained reentrant tachycardia in these patients. This report deals with the observations made in these five patients.

Methods

Right heart catheterization was performed with patients under local anes- thesia and in the postabsorptive, nonsedated state. The nature of the proce- dure was explained to all patients and signed consent was obtained. Elec- trode catheters were percutaneously introduced into peripheral veins and fluoroscopically positioned to record atria1 and His bundle electrograms as previously described. l3 Atria1 pacing was accomplished using a digital stimu- lator capable of delivering rectangular impulses of 1.5 msec duration at an adjustable milliamperage. The rate of atria1 pacing was gradually increased (in increments of 10 beats/min) to r es sufficient to produce A-V nodal Wenckebach cycles. During pacing-n led A-V nodal Wenckebach cycles, the stimulator was periodically turm lff to permit observation of subse- quent spontaneous events. The atria1 t rastimulus technique was employed to determine refractory periods of the A-V conduction system.14 A premature

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A-V NOOAL REENTRANT TACHYCARCNA AFTER ATRCPIW-AUHTAR ET AL.

atria1 beat (AZ) was introduced after every eighth sinus or paced beat (Al-Al) until atria1 refractoriness occurred.

Standard electrocardiographic leads I, II, III and VI, in- tracardiac electrograms and time lines generated at 10 and 100 msec were displayed on a multichannel oscilloscope and recorded on magnetic tape. The records were subse- quently recorded on photographic paper at a speed of 150 mm/set. After completion of the control studies 0.5 mg of atropine was given intravenously and the studies were re- peated 10 minutes after drug administration. All equip- ment was carefully grounded. The procedure was well tol- erated by all patients.

Definition of Termr15~16

The A-H interval was measured from the onset of the low atria1 electrogram (on the recording of the His bundle electrogram) to the beginning of the His bundle deflection and was used as an approximation of A-V nodal conduction time (normal for our laboratory 60 to 140 msec).

The H-V inter& was similarly measured from the onset of the His bundle deflection to the beginning of ventricular activation and was taken as an approximation of His-Purk- inje conduction time (normal for our laboratory 30 to 55 msec).

The effective refractory period of the atrium is defined as the longest &-S2 interval in which $2 fails to depolarize the atrium, S representing the artificial stimulus.

The effectiue refractory period of the A-V node is the longest atria1 coupling interval (Al-A2 interval) in which A2 blocks in the A-V node.

The functional refractory period of the A-V node is the shortest HI-HZ interval in response to a full range of Al-As intervals to the point of atria1 refractoriness.

Atria1 echo beat (A-V nodal reentrant atria1 echo beat, Ae) is the reentrant atria1 beat with a low to high sequence of atria1 activation following induced atria1 beats associated with a critical degree of A-V nodal conduction delay (A-H interval).

Results

Clinical and electrophysiologic data are summa- rized in Tables I and II. None of the patients had a

TABLE II

TABLE I

Clinical Data -~-

Case Age (vr) Diagnosis of Resting

no. & Sex Heart Disease Electrocardiogram

1 15M None 1” A-V block, normal QRS complex

2 60M Arteriosclerotic Anterior myocardial

infarction; right

bundle branch block;

left anterior

hemiblock

3 75M Arteriosclerotic Left bundle branch

block

4 56M None Normal

5 6OF None Normal ---

history suggestive of tachycardia or electrocardio- graphic evidence of a supraventricular tachyarrhyth- mia or the Wolff-Parkinson-White syndrome. No pa- tient was taking any cardioactive medications. The well known effects of atropine on sinus rate and A-V nodal conduction were observed in all five patients. The average decrease in sinus cycle length after ad- ministration of atropine was 164 msec (range 60 to 300 msec), representing an average decrease of 21 percent from control values. All patients manifested a decrease in the sinus A-H interval after administra- tion of atropine (average decrease 28 msec). Results obtained in individual patients are as follows:

Case 1 (Fig. 1 and 2): In this 15 year old boy with first degree heart block of uncertain origin neither atrial echo beats nor A-V nodal reentrant tachycardia could be elicited during control studies but could readily be induced after administration of 0.5 mg of atropine. During control stud- ies (Fig. 1, panels A and B) the longest A-H interval that could be achieved during premature atrial stimulation was 280 msec (panel A). The effective refractory period of the

Electrophysiologic Data (msec) Before (B) and After (A) Administration of Atropine

Case no. State

Sinus Rhythm

Cycle A-H Length Interval

Critical A-H Interval

For Supra- For Atrial ventricular

Echu Beats Tachycardia

Longest A-H Interval __-

During During Continuous Antegrade

Atrial Refractory Pacing Periods

1 I3 A

2 B A

3 B A

4 B A

5 B A

680 250 620 165

900 100 600 85

780 105 600 85

-

420

370-390 275-285

295-465

850 70 650 60

240-260

680 100 430-600 600 90 500

- 290

440-575 365

- 405 275-400 400

- 465 300-380 380

- 240 240-260 260

- 560 500-600 600

280

575

390 285

400 350

260

150

600 300

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A-V node was determined to be 580 msec (panel B). After administration of atropine (panels C and D) the effective refractory period of the A-V node significantly shortened, thereby permitting more premature atria1 beats to be con- ducted with longer A-H intervals. Sustained A-V nodal reentrant tachycardia consistently occurred after A-H in- tervals of 440 to 575 msec. Termination of tachycardia by a

single properly timed premature atria1 depolarization is il- lustrated in Figure 2.

Case 2 (Fig. 3): In the control period, only infrequent single atria1 echo beats occurred after A-H intervals of 370 to 390 msec induced by premature atria1 stimulation; these beats did not occur at similar A-H intervals during pacing-

A &__

CONTROL - A

T,,‘,, /,,,/ ,, //, ,,,,, ,, , 1 1 C AFTER ATROPINE 0.5mg.W

59 735 ’ I) ” ”

$1300 /_ li

600 A 620 A

&I ‘620 A,29dA2 650 ,Ae 520. As 520. Ae 520” Ae

FIGURE 1. Case 1. Supraventricular tachycardia after administration of atropine. Tracings in each panel (from top to bottom) are: electrocardiographic leads II (2) and V,, a high right atrial electrogram (HRA), His bundle electrogram (HBE) and time lines (T) at 10 and 100 msec. S denotes stimulus artifact. During sinus rhythm the A-H interval is abnormally prolonged at 250 msec and the sequence of atrial activation is from the high to the low atrium. In the control period a prema- ture atrial beat (AZ) coupled to a preceding sinus beat (A,) at an interval of 590 msec is conducted with an AZ-H2 interval of 280 msec. At a slightly closer AI-A2 interval of 580 msec (panel B), A2 is blocked in the A-V node and a sinus escape beat follows. Administra- tion of atropine resulted in shortening of the sinus cycle length and the A-H interval and a marked de- crease in the effective refractory period of the A-V node as evidenced by the ability of relatively earlier premature atrial beats to conduct to the bundle of His (panels C and D). The decrease in the A-V nodal ef- fective refractory period after administration of atro- pine is accompanied by achievement of longer A-H in- tervals (panels C and D). At critically long A-H intervals a sustained supraventricular tachycardia occurred (panel D). Note the low to high sequence of atrial acti- vation (Ae) and the inverted P wave in lead II during su- praventricular tachycardia. Ae = atrial echo beat.

~,,,,,,,,,,,,,,,,,,,,,,,,,,, /(,/,I

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FIGURE 2. Case 1. Termination of supraventricular tachycardia. In panel A, a premature atrial beat is delivered at an Ae-A2 interval of 280 msec and does not terminate the tachycardia. At a closer coupling interval of 265 msec (panel B), A2 successfully ter- minates the tachycardia and sinus rhythm is restored.

induced A-V nodal Wenckebach cycles. After administra- tion of atropine, sustained A-V nodal reentrant tachycardia regularly occurred at similar or shorter A-H intervals pro- duced either by premature atria1 depolarizations or by pac- ing-induced A-V nodal Wenckebach cycles.

Case 3 (Fig. 4): During control studies in this patient, A-V nodal reentry, as manifested by single or two consecu- tive atria1 echo beats, could easily be elicited, but sustained A-V nodal reentrant tachycardia never occurred. After ad- ministration of atropine, sustained reentrant tachycardia was regularly initiated at the same A-H intervals that pro- duced only one or two echo beats in the control period.

Cases 4 and 5: A-V nodal Wenckebach cycles induced by atria1 pacing after administration of atropine resulted in sustained supraventricular tachycardia at the same period of A-V nodal conduction delay (A-H interval) that gave rise to only single atria1 echo beats during the control period (Table II). The critical A-H intervals necessary for demon- stration of A-V nodal reentry, although obtained with rapid atria1 pacing, could not be attained during atria1 premature coupling in these two patients.

Discussion Mechanism of reentrant phenomenon in each

case: It has been well established that A-V nodal reentry in the form of atria1 echo beats requires a

, B ARwATRopNO5m8lV CL340

:-

vl ttw

** n IL!n 225 !&?o

T 190 195 ,205 2l5

FIGURE 3. Case 2. Supraventricular tachycaidia after administration of atropine. Panel A shows 3:2 A-V nodal Wenckebach cycles at a paced atrial cycle length of 400 msec. The A-H intervals of the first and second conducted beats measure 125 and 365 msec, respec- tively, and the third atrial beat blocks in the A-V node. The atrial stimulus is omitted after the last conducted beat of the second Wenckebach cycle following which a sinus escape beat occurs. After administration of atropine A-V nodal conduction of the Wenck- ebach type occurred at a paced atrial cycle length of 340 msec (panel 6). The last (fifth) atrial paced beat conducts with an A-H in- terval of 360 msec and is followed by a sustained A-V nodal reentry. This figure also demonstrates spontaneous termination of supraven- tricular tachycardia. From the onset of the tachycardia there is a progressive decrease in the Ae-H interval (panels B and C are con- tinuous) from 255 msec to 205 msec. There is a corresponding in- crease in the H-Ae interval and a final block of the impulse in the ret- rograde limb of the reentry circuit, and sinus rhythm ensues.

critical range of antegrade A-V nodal delay, most often elicited by premature atria1 stimulation. With- in the context of our present limited understanding of the reentrant phenomenon it is postulated that a requisite antegrade delay is necessary to allow recov- ery of the retrograde limb of the reentrant circuit, which may lead to reexcitation of the atrium. Within the limits of this #currently accepted concept the fol- lowing explanations are offered for the results ob- tained in these cases.

In Case 1, a prolonged effective refractory period of the A-V node prevented closely coupled atria1 pre- mature beats from being conducted with sufficiently long antegrade A-V nodal conduction time (A-H in- tervals) to permit recovery of the retrograde limb. This situation was reversed by atropine, which de- creased the effective refractory period of the A-V node so that more closely coupled atria1 premature beats could be conducted. These beats were associ- ated with critically long A-H intervals and the neces- sary balance between conduction and refractoriness within the limbs of the reentrant circuit was achieved.

In Cases 3 to 5, most often only single and occa- sionally two consecutive atria1 echo beats were elic- ited in the control period within a critical zone of

A CONTROL

FIGURE 4. Case 3. Supraventricular tachvcardia after administration of atropine. In panel A’a premature atriaibeat (A*) is coupled to the preceding sinus beat at an AI-A2 interval of 420 msec. A2 conducts with an AZ-H* interval of 320 msec and initiates unsustained A-V nodal reentry. The reentrant impulse conducts in antegrade fashion to the bundle of His with an AsH interval of 440 msec, then con- ducts back to the atrium and finally blocks in the antegrade limb. The H-Ae interval for the two reentrant beats is constant at 40 msec. After administration of atropine (panel B) sustained A-V nodal reen- try is initiated at a similar degree of A-V nodal delay (AZ-H* interval 320 msec) as in the control period. After an initial variation, the Ae-H interval stabilizes at 375 msec. The H-Ae interval remains un- changed at 40 msec. Subsequent atrial stimuli (panel B) are for the most part ineffective and were delivered inadvertently. The third stimulus captures the high right atrium and results in fusion activation of the right atrium (low atrial electrogram; that is. Ae occurs at the expected time) (A-Ae interval 480 msec). This has no effect on the supraventricular tachycardia.

A-V NODAL REENTRANT TACHYCARDIA AFTER ATRDRNE-AKHTAR ET AL.

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A-V NODAL REENTRANT TACHYCARDIA AFTER ATROPINE-AKHTAR ET AL.

A-H delay. Failure of the atria1 echo beats to conduct to the His-Purkinje system suggests that the ante- grade limb of the A-V nodal reentrant pathway was refractory to the reciprocating impulse and therefore sustained reentry did not occur. The occurrence of sustained reentry after administration of atropine, which was initiated at levels of A-H delay compara- ble to those of the control period, implies that atro- pine decreased refractoriness of the antegrade limb to a degree that permitted continuous reciprocation. A decrease in A-V nodal refractoriness is a well known effect of the drug. Whether the retrograde limb was equally or unequally affected by atropine can only be conjectured. However, atropine did bring about the necessary balance between conduction and refractoriness within the reentrant circuit.

In Case 2, sustained supraventricular tachycardia occurred after administration of atropine at A-H in- tervals significantly shorter than those that in the control period resulted in either single or no atria1 echo beats. Since sufficient antegrade A-V nodal delay (that is, longer A-H intervals) was achieved during the control period, it appears that improved conduction and shortening of refractoriness of only the crossover or retrograde pathway, or both, after administration of atropine were responsible for creat- ing the balance necessary for the occurrence of sus- tained reentry. This possibility is also suggested by the mechanism of spontaneous termination of supra- ventricular tachycardia (Fig. 3). The initiation of sus- tained reentry at shorter A-H intervals after adminis- tration of atropine further attests to the importance of a balance between conduction and refractoriness in the limbs of a reentrant circuit.

Atropine and reentry: The possibility that atro- pine caused sustained reentry by changing atria1 re- fractoriness can be summarily dismissed for the fol- lowing reasons:

1. Small doses of atropine, as used in this study. produced no significant changes in atria1 refractori- ness as tested by the extrastimulus method.” After administration of atropine the effective refractory period of the atrium increased by 10 msec in Cases 1 and 3, decreased by 10 msec in Cases 2 and 5 and did not change in Case 4.

2. In four of five cases (Cases 2 to 5) atria1 echo beats did occur in the control period and in Cases 3

to 5 the atria1 echo beats were not followed by His bundle potentials, thus suggesting that the A-V node, not the atria, was refractory.

Although administration of small doses of atropine resulted in sustained A-V nodal reentry in these 5 pa- tients, findings were not similar in the other 17 pa- tients”,12 who received the same amount of drug. There are several possible explanations for these dif- ferences: (1) Only 5 patients had the potential for de- velopment of reentrant supraventricular tachycardia that was unmasked by atropine; (2) in the other 17 patients the dose of atropine was either too small or too large; or (3) atropine simply did not produce the necessary balance of conduction and refractoriness between the antegrade and retrograde limbs of the reentrant circuit in these 17 patients.

Clinical implications: The results of this study help to elucidate some underlying mechanisms re- sponsible for the success of therapeutic agents, such as digitalis and propranolol, in the management of patients with supraventricular tachycardia. Both dig- italis and propranolol are known to prolong refracto- riness of the A-V node and therefore may totally abolish manifestations of A-V nodal reentry.17-lg These changes could result from prolongation of A-V nodal conduction and refractoriness in one or more sites in the reentrant circuit-the antegrade or retro- grade limbs or crossover tracts-so that the prema- ture atria1 beats fail to induce the echo response. In some patients single or multiple atria1 echo beats may still be demonstrable after administration of these drugs although sustained A-V nodal reentry may not occur if the necessary balance between con- duction and refractoriness within the various limbs of the reentrant circuit is sufficiently altered by the therapeutic agents. Finally it must be pointed out that at times, these and other drugs may show what appear to be paradoxical effects on the reentrant phenomenon, We have observed in some patients A-V nodal reentrant atria1 echo beats occurring only after administration of digitalis or propranolol whereas none were seen during the control period (unpublished observations). Likewise, it is conceiv- able that atropine may prevent sustained reentry in some patients with supraventricular tachycardia by altering the critical balance of conduction and refrac- t,oriness within the A-V node.

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A-V NODAL REENTRANT TACHYCARDIA AFTER ATROPiNE-AKHTAR ET AL.

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