cardiac asystole- a manifestation of neurally mediated hypotension-bradycardia. jacc 1989

8/10/2019 Cardiac Asystole- A Manifestation of Neurally Mediated Hypotension-bradycardia. JACC 1989

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JACC Vol. 14, No. 7

Decembe r 1989: 1626-32

MILSTEIN ET AL.

1627

NEURALLY MEDIATED CARDIAC ASYSTOLE

within the same time frame. In each group, there were four

men and two women, ranging in age from 16 to 59 years

(mean 35). Group I consisted of six patients who presented

with sudden unexpected cardiovascular collapse, apparently

in association with cardiac asystole, of sufficient duration to

result in initiation of resuscitative mea sures. Group II in-

cluded six patients with a history compatible with recurrent

but self-limited neurally mediated syncope (for example,

vasovagal syncope) without evident asystole and in whom

conventional electrophysiologic evaluation failed to detect

an abnormality of sufficient mag nitude to account for syn-

cope. Group III consisted of six patients with recurrent

syncope in whom positive findings during conventional

electrophysiologic testing provided a basis for the syncopal

symptoms. None of these patients had been taking cardio-

active medication at the time of syncope.

For purposes of this study, an asystolic pause was defined

as absence of perceptible pulse or ECG documentation of

cardiac asystole, or both, for an interval 2 12 s, accompanied

by loss of consciou sness and postural tone.

Diagnostic evaluation.

All patients provided a complete

medical history and underwent physical examination and

routine laboratory testing. V ital signs were recorded in all

patients, and individual right and left carotid sinus massage

was performed during continuous ECG monitoring. M-mode

and two-dimensional echocardiography as well as neurologic

consultation was obtained in all patients.

Electrophysiologic study. After

informed consent was ob-

tained, all patients un derwe nt invasive electrophysiologic

evaluation in the postabsortive state using mild sedation

(diazepam, 5 mg intravenously). All cardioactive medica-

tions were discontinued for at least five half-lives before

electrophysiologic study. Three 6F quadrip olar electrode

catheters were inserted into the right femoral vein, using the

percutaneous approach and modified Seldinger technique,

and positioned at the high right atrium, at the right ventric-

ular apex and across the tricuspid valve for His bundle

recording, respectively. An intraarterial can nula was placed

percutaneou sly into the femoral artery to monitor arterial

pressure. Surface E CG leads I, II, III, V, and V,; intracar-

diac recordings from the high right atrium, right ventricle

and His bundle position along with arterial blood pressure

were simultaneously displayed on an Electronics for Medi-

cine VR16 recorder and recorded simultane ously on fre-

quency modulation tape. Recordings were obtained at a

speed of 50 or 100 mm/s. Pacing w as accomplished by means

of a custom-designed programmable stimulator with opti-

cally isolated outputs. The stimulus duration was 2 ms, and

the amplitude was twice diastolic threshold.

Baseline sinus cycle length and conduction intervals were

recorded. Sinus node function was assessed by determining

sinus node recovery time at a pacing cycle length ranging

from 300 to 700 ms at 50 ms decrements. The subseque nt 10

postpacing intervals were analyzed for the presence of

secondary p auses. Atrioventricular node and infranodal con-

duction and refractoriness characte ristics were determine d

both by right atria1 pacing at progressively shorter cycle

lengths and by extrastimulus testing using a drive train of

eight cycles at a basic p acing length of 600 and 400 ms. Single

atria1 extrastimuli were introduced at 10 ms decrements until

refractoriness was reached.

The protocol for ventriculur electrical stimulation in-

cluded scanning of diastole with single, double and triple

ventricular extrastimuli introduced after an eight beat ven-

tricular drive train, utilizing a basic pacing cycle length of

600 and 400 ms. Ventricular extrastimulus testing was per-

formed at both the right ventricular apex an d outflow tract.

The extrastimu li coupling intervals were progressively short-

ened by 10 ms until ventricular refractoriness was reached.

Upright tilt.

After conventional electrophysiologic test-

ing was completed, ba seline measurements of heart rate and

blood pressure were recorded with the patient in the supine

position. Usin g an electronically controlled tilt table with a

foot board for weight bearin g, up right tilt (80 head-u p) (4,5)

was then performed for up to IO min, with a positive

response being defined as developm ent of syncope. If the

patient did not have a positive response during baseline

conditions, he or she was lowered to the supine position at

the end of the 10 min period. After a rest period of 5 min,

upright tilt was repeated during continuous intravenous

isoproterenol infusion at successive incremental doses of 1

and, if necessary, 3 pg/m in. During each step of the proto-

col, the patient was returned to the supine position either

when a positive response was achieved or after 10 min of

upright tilt. An equilibration period of 5 min, during which

heart rate and blood pressure were allowed to achieve a

stable baseline value, was introduced between each succes-

sive increase in isoproterenol dose.

Statistical analysis.

Group data are reported as mean

values i SD. lntergroup comparisons were made using

Students

t

test. with a p value ~0.05 being considered

indicative of a statistically significant difference.

esults

linical and Electrophysiologic Findings

Group I: patients presenting with cardiovascular collapse

and apparent asystole. Patient 1

had recurrent episodes of

syncope associated with hypotension -bradycardia syn-

drome. Durin g one of the episodes, his wife (a trained

intensive care unit nurse) was unable to detect any pulse for

a 20 s period. T he patient recovered after cardiopulm onary

resuscitation was initiated. Patient 2 had a history of recur-

rent syncope a nd presented with cardiovascular collapse,

during which 22 s of cardiac asystole was fortuitously

documented by ambulatory ECG monitoring. Patient 3 was a

well trained athlete who collapsed while running. A cardiol-

ogist witnessing the scene initiated cardiopulmonary resus-


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628

MILSTEIN ET AL.


JACC V ol. 14, No. 7

December 1989: 1626-32

~

\

\

.

t

p 0.005

b

Figure 1. Changes in mean arterial pressure (left

panel) and heart rate (right panel), comparing

measurem ents at 1 min after assumption of up-

right posture with those at the time of syncope in

six Group I patients w ith cardiovascular collapse

and apparent asystole. Mean arterial pressure

decreased from 70 to 24 mm Hg, and the chrono-

tropic response was inadequate in five patients

with a decrease in heart rate from 97 to 55

beats/mitt. Circles = tilt alone; triangles = tilt

plus isoproterenol infusion a t 1 pg/min; squa res =

tilt

t

isoproterenol infusion at 3 pg/min.

-

TILT

SYNCOPE

TILT SYNCOPE

1 min 1 min

ASYSTOLIC

citation after confirming that the patient had no pulse and

was apneic. Patient 4, a competitive swimmer, sustained a

cardiac arrest while swimming strenuously and dropped to

the bottom of the swimm ing pool. After rescue, cardiopul-

monary resuscitation was initiated after it was confirmed

that she had no pulse and was apneic. Patient 5 was a

medical resident who was running to an emergency call

when he suddenly collapsed. Cardiac asystole was docu-

mented by ECG an d he recovered after a period of cardio-

pulmona ry re suscitation. Patient 6 had a history of recurrent

syncopal events and presented after an episode of cardio-

vascular collapse, during which 15 s of asystole was docu-

mented in a hospital emergency room.

Five of these six patients had no evidence of underlying

structural heart disease on the basis of history, ECG and

M-mode and two-dimensional echocardiography. Patient 6

had a past history of an uncomplicated acute anterior myo-

cardial infarction 13 years before the first syncopal eve nt. A ll

six patien ts ha d normal findings on electrophysiologic eval-

uation.

Group

II:

patients with syncope and normal conventional

electrophysiologicstudy.

This group of six patients had no

structural heart disease and had normal electrophysiologic

evaluation. They underwent tilt evaluation according to a

protocol for patients w ith recurrent unexp lained syncop e.

Group III: patients with syncope and diagnostic conven-

tional electrophysiologicstudy. Two of the six patients had

pre-excitation syndrome, two had coronary artery disease,

one had nonischemic cardiomyopathy and one had no evi-

dence of structural hea rt disease. Electrophysiologic find-

ings that appeared to indicate the cause of syncope were

orthodromic rec iprocating tachycardia with marke d hypo-

tension in one patien t, atria1 fibrillation with rapid ventricu-

lar response and associated hypotension in two patients,

infra-His bundle block associated with a long HV interval

and bifascicular bundle branch block in one patient and

inducible polymorphic ventricular tachycardia in two pa-

tients.

esponse to Upright Tilt

Group

I:

patients presenting with cardiovascularcollapse

and apparent asystole. All

six patients presenting with ap-

parent asystolic cardiovascular collapse developed syncope

during upright tilt provocation. In each case, compared with

a baseline m ean arterial pressure measured 1 min after

assumption of upright posture, syncope wa s associated with

a marked decrease in mean arterial pressure (from 70 ? 8

mm Hg at 1 min of tilt to 24 f 6 mm Hg at the time of

syncope, p < 0.001) Fig. 1). The chronotropic response to

this degree of hypotension was inadequate and directionally

inappropriate in five of the six patients, decreasing from 90 +

33 beats/min at 1 min of tilt to 3 9 2 19 beats/min during the

syncopal spell (Fig. 2). Two patients (Cases 2 and 5) mani-

fested 16 and 20 s of asystole, respectively (Fig. 2). One

patient (Ca se 3) exhibited a positive chronotropic response

during tilt provocation, but nonetheless became m arkedly

hypotensive and syncopal.

Three patients (C ases 1,4 an d 6) became syncopal during

tilt alone (at 4,3 and 2 min of tilt, respectively). Two patie nts

(Cases 2 and 3) tolerated tilt in the baseline state, but

exhibited syncope when tilt was performed during isoproter-

enol infusion at

1

pg/min. The latter patients became synco-

pal at 5 and 2 min of tilt, respectively. One patient (Case 5)

tolerated baseline upright tilt and tilt during isoproterenol

infusion at 1 pg/min, but developed syncope at 2 min during

combined tilt and isoproterenol infusion at 3 pg/min.


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JACC Vol. 14, No. 7

Decembe r 1989: 162632

MlLSTEIN ET AL.

1629


l-2

.

RV

.

I I

HB

1. f *

Group II: patients with syncope and negative conventional

electrophysiologic study.

All six patients with a history sug-

gestive of self-limited neurally mediated syncope and nega-

tive conventiona l electrophysiologic test results manifested

syncope in


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163

MILSTEIN ET AL.

JACC Vol. 14 No. 7


December 1989: 162632

60

0-

TILT SYNCOPE

TILT

1

m n

1

m n

EP NEGATIVE

MNCOPE

mm Hg) with a directionally appropria te chronotropic re-

sponse (121 ? 7 versus 133 ? 7 beats/min) (Fig. 4).

Intergroup comparison of tilt response. Maxim al changes

in mean arterial pressure and heart rate from values at 1 min

of upright tilt to the moment of syncope in patients in Groups

I and II and from the 1st to the 10th min of upright tilt in

patients in Group III differed dramatically (Fig. 5). Patients

in Groups I and II experienced marked hypotension-

bradycardia; mean arterial pressure decreased 4 6 ? 9 and 40

+ 9 mm Hg and heart rate decreased 44 ? 28 and 49 ? 12

beats/m in in Group I and Group II, respectively. Con-

versely, patients in Group III exhibited only a modera te

decrease in arterial pressure (14 ? 5 mm Hg) in conjunction

with an increase in heart rate (14 ? 8 beatslmin).

The difference in maximal mean arterial pressure and

Figure3. Changes n m ean arterial pressure (left panel)

and heart rate (right panel), comparingmeasurements

from 1 min after assumptionof upright posture with

those at the time

of syncope in six Group II patients

with syncope and normal findings on electrophysio-

logic (EP) evaluation. There is a marked d ecrease in

mean arterial pressure from 71 to 31 mm Hg. The

chronotropic response to this degree of hypotension is

inadequate, and the heart rate decreases from 1 02 o 54

beatslmin. Symbols as in Figure 1.

heart rate changes during upright tilt between Group I and

Group II patients was not statistically significant. However,

both mean arterial pressure and heart rate changes during

upright tilt differed significantly (p < 0.001) in Group I and

Group III patients.

Discussion

Tilt-induced hypotension-hrady cardia in patients with syn-

cope. This study demonstrates that patients with suspected

or documented cardiac asystole and normal conventional

electrophysiologic evaluation exhibit a susceptibility to tilt-

induced neurally mediated hypotension-bradycardia. In-

deed, on occasion, head-u p tilt resulted in a prolonged

asystolic event. Furthermore, electrophysiologic and tilt

140 --s 60-- 1 / 1

E

120 --

IF

Figure 4. Changes in mean arterial pressure (left

L

1

panel) and heart rate

(right panel), comparing

L

2 60--

E

100 --

measurements at 1 min after assumption of up

right posture w ith those at 10 min of upright

t3

e

80 --

g

E

posture in the six Group III patients with syncope

2

and diagnostic electrophysiologic (EP) evalua-

6 40 --

s 60 --

tion. During continuous isoproterenol infusion

at

5

I

3 pg/min, there is a moderate but consistent

3

40 --

decrease in mean arterial pressure from 85 to

71

I 2o--

mm Hg. The chronotropic response to this degree

20 --

of hipotension is adequ ate, and the heart rate

p-0.c.X

p-0.ocU

increases from 121 to 133 beats/mitt. Symbols as

0 I I 0

I I I

in Figure 1.

TILT

TILT

T I L T

TILT

1

m n

10

m n

1 m n 1 0 m in

EP POSITIVE


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1632

MILSTEIN ET AL.


JACC

Vol. 14, No. 7

December 1989:162 32

infrequently exhibit unanticipated hypotension-bradycardia

when undergoing the tilt test protocol described here (4).

Because cardiac asystole may be a manifestation of

neurally mediated hypotension-bradycardia syndrome, this

possibility should be considered when studying survivors of

sudden death. Immediate identification of these patients

poses a management dilemma. At first, it may seem reason-

able to consider permanent pacemaker implantation in indi-

viduals with recurrent neurally m ediated syncopal episodes

in an attempt to avert the potential fatality related to this

syndrome. However, as demonstrated by Almquist et al.

(23), mainte nance of heart rate doe s not necessarily reverse

hypotension in association with the vasodep ressor response

despite preven ting th e bradycardia. In fact, Patients 2 and 6

in the asystolic group of patients (Group I), in the present

study continued having syncope despite implantation of a

permanent pacemaker (before referral for study).

Recent preliminary reports from this laboratory (24,25)

suggest that beta-adrenergic blocking agents or drugs with

combined anticholinergic and negative inotropic effects

(such as disopyramide) may be useful in preventing tilt-

induced hypotension -bradycardia and recurrent syncope. It

seems reasonable to postulate that this therapeutic approach

might be beneficial in patients with cardiac asystole, normal

findings on electrophysiologic evaluation and tilt-induced

hypotension-b radycardia. Howev er, careful clinical studies

are essential before such a treatmen t strategy ca n be recom-

mended.

We are indebted to the staff of the Cardiac Catheterization Laboratory for

their assistance and to W endy Marku son for assistance in the preparation of

the manuscript.

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cardiac asystole- a manifestation of neurally mediated hypotension-bradycardia. jacc 1989

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