Download in Elderly People

Significance of Chronic Sinus Bradyeardia
in Elderly People
By NEIL S. AGRUSS, M.D., ELAINE Y. RosIN, M.D., ROBERT J. ADOLPH, M.D.,
AND
NOBLE
0.
FOWLER, M.D.
SUMMARY
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It may be difficult to evaluate sinus bradyeardia in the elderly since sinus rates
below 50 beats/min may occur normally with aging. Seven asymptomatic bradyeardic
subjects (heart rates 41-51 beats/min), ages 67-79 years, with no evidence of impaired
cardiac performance and taking no drugs, were compared with four age-matched controls (heart rates 60-84 beats/min). Autonomic function was tested with the Valsalva
maneuver, amyl nitrite inhalation, methoxamine infusion, head-up tilt, and atropine
intravenously (2 mg).
Cardiac index at rest was normal in bradyeardic subjects (2.4 0.1 SEM); increased cardiac stroke volume (SV) compensated for the slow heart rate. With supine
bicycle exercise, increase in cardiac output per 100 ml increase in oxygen consumption
was normal in bradyeardics (885 + 60 ml compared to 907
171 ml in controls).
This exercise response was achieved mainly by increased SV in bradyeardics and by
increased heart rate in controls. Significant increases in cardiac output occurred with
both atropine and atrial pacing in bradyeardics, but not in controls. Autonomic impairment was not found. Increased vagal tone in bradyeardics was suggested by a
lesser heart rate response to exercise and passive tilting.
Hence, a heart rate below 50 beats/min in elderly people does not necessarily indicate depressed cardiac performance. Further evaluation of the significance of bradycardia in these subjects requires long-term observation.
Additional Indexing Words:
Heart rate
Cardiac output
Response to atrial pacing
Response to atropine
Autonomic function
Exercise response
RE'esponse to passive head-up tilt
S INUS bradyeardia in the adult may be
defined as a heart rate below 60 beats/
min with a normal sequence of cardiac
activation. Recent reports have emphasized L
chronic sinoatrial bradyeardia as a cause of
From the Division of Cardiology, Department of
Medicine, University of Cincinnati College of Medicine, Cincinnati General Hospital, Cincinnati, Ohio
45229.
Supported in part by the National Institute of
Health Grants HE-06307 and HE-5445, and the Heart
Association of Southwestern Ohio.
Address for reprints: Neil S. Agruss, M.D., Cardiac
Research Laboratory, H/3, Cincinnati General Hospital, Cincinnati, Ohio 45229.
Received: March 2, 1972; revision accepted for
publication May 31, 1972.
924
cerebral dysfunction, syncope, and other
symptoms of diminished cardiac output or
regional blood flow.'-6 Most patients reported
have been over 50-60 years of age, with resting
heart rates near 40-50 beats/min. Associated
cardiac rhythm and AV conduction disturbances have been frequent. Without these a
decision as to whether or not sinus bradyeardia causes symptoms may be difficult, since
dizziness, fatigue, weakness, exertional dyspnea and syncope can result from a variety of
noncardiac disorders in the elderly, and the
resting heart rate tends to diminish with
age.7
This paper reports hemodynamic data
obtained from seven elderly asymptomatic
bradyeardic subjects during supine rest
Circulation, Volume XLVI, November 1972
925
SINUS BRADYCARDIA IN THE ELDERLY
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supine bicycle exercise, and during sustained
increase of the heart rate by atrial pacing.
Autonomic nerve function was evaluated from
the response of the heart rate and blood
pressure to head-up tilt, Valsalva maneuver,
amyl nitrite inhalation, intravenous methoxamine, and a 2.0 mg intravenous dose of
atropine. The data were compared to those
obtained from a group of age-matched con-
and were averaged. No more than 2 min elapsed
between duplicate cardiac output determinations.
Systemic arterial and right atrial pressures were
recorded on an Electronics-for-Medicine photographic recorder using Statham P23dB pressure
transducers. Gauges were leveled 10 cm above
the table top for all supine studies, and at the
level of the midright atrium, as determined
fluoroscopically, during head-up tilt. A bipolar
electrode catheter* was used for pacing the right
trols.
Following placement of all catheters the resting
cardiac output (CO), heart rate (1HR1), and
brachial artery (BA) pressure were measured.
The HR and BA pressure xvere then continuously
recorded during the Valsalva maneuver,9 during
inhalation of amyl nitrite, and following a 2-min
intravenous infusion of methoxamine, 0.06 mg/
kg. The subject was then tilted head-up to a 450
angle with the horizontal. CO, HR, and BA
pressure measurements were made after 3 min of
tilt. Following return to the horizontal position
and after a 10-min rest, the atrial rate was slowly
increased by atrial pacing. After at least 5 min
had elapsed at pacing rates of approximately 70
and 90 beats/min in the bradycardic subjects,
and 90 beats/min in controls, the CO, HR, and
BA pressure were measured. The atrial rate was
then increased by 10 beats/min increments to 150
beats/min or until second degree AV block appeared. The postpacing recovery time of the
sinus node pacemaker was observed following
sudden cessation of the highest pacing rate
attained. The subjects then exercised in the
supine position on a bicycle ergometer, maintaining a work rate of 150 kg-meters/min (1200 ft
lbs/min). This work level increased oxygen
consumption two and a half to three times
control. During the sixth and seventh min of
exercise expired air was collected and CO, HR,
and BA pressure were measured. After the
subjects rested 15 min, the circulatory response to
exercise at a controlled heart rate was measured
in four of the seven bradyeardic subjects. The
resting HR was increased by atrial pacing to rates
slightly above those attained spontaneously dur-
Methods
The bradycardic subjects were seven men, ages
67-79 years, with resting heart rates between 41
and 51 beats/min. Each had chronic sinus
bradyeardia as determined from two or more
electrocardiograms recorded over a 6-month, or
longer period of time. Additional electrocardiographic findings were: first degree AV block in
two subjects (PR interval-0.24 sec in each);
first degree AV block (PR interval 0.48 sec) and
left anterior hemiblock in one subject; intermittent RBBB (unrelated to heart rate) in one
subject; and possible left ventricular hypertrophy
(voltage criteria only) in one subject. No subject
at any time had electrocardiographic evidence of
an atrial or ventricular tachyarrhythmia, SA
block, sinus arrest, AV junctional rhythm, or
second or third degree AV block. All seven
subjects were asymptomatic and had no history of
heart disease or hypertension; none was taking
medication. No subject had athletic training or
was engaged in a prescribed exercise program.
Chest roentgenograms were normal in each
subject, and none had clinical or laboratory
evidence of impaired cardiac reserve, hypothyroidism, diabetes, chronic renal disease, neurologic disease, malignancy, hyperlipidemia, anemia,
or electrolyte disturbance. Four healthy subjects,
three men and one woman, ages 61-79 years, with
resting heart rates between 60 and 84 beats/min,
served as the control group. Each had normal
electrocardiograms and chest X-rays; none was
taking medication. Informed consent was obtained from all 11 subjects before the study. On
the day before study each subject was acquainted
with the equipment and procedures to be
employed, and trained in the Valsalva maneuver.
All subjects were studied in the postabsorptive
state without receiving premedication. Cardiac
outputs were measured by the dye-dilution
technic (indocyanine green). Methods for determining heart rate, stroke volume, and oxygen
consumption have been previously reported.8
Duplicate cardiac output determinations during
rest, head-up tilt, exercise, various rates of atrial
pacing, or following atropine agreed within 10%
Circulation, Volume XLVI, November 1972
atrium.
ing
exercise; exercise
was
then performed
as
before. The CO, HR, and BA pressure were again
measured during the seventh minute of exercise.
Following a 15-min rest period, each subject
received 2.0 mg of atropine intravenously in 2
min. Four minutes after the injection CO, HR,
and BA pressures were again measured. Resting
CO, HR, and BA pressure measurements were
obtained in each subject before head-up tilt,
*NBIH Catheter, U. S. Catheter &
Corporation, Clens Falls, New York.
Instrumiient
AGRUSS ET AL.
926
before atrial pacing and exercise studies, and
before atropine.
Results
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Individual and group mean data for both
the bradyeardic and control subjects are
shown in the figures. The mean age and body
surface area were similar in both groups.
Right atrial pressure was normal and not
significantly different in the two groups at rest
and during subsequent interventions. Other
than the HR and stroke index (SI), the
resting baseline data for the two groups were
similar (figs. 1 and 2). The mean heart rates
of the two groups differed significantly (P<
0.001). There was no significant difference in
mean resting cardiac index (fig. 1). Cardiac
index (CI) was similar to that reported for
normal subjects of similar age.7 10 The difference in SI between the groups was statistical-
PACING
CONTROLS
BRADYCARDIGS
0@
3.0
0
I, I
ly significant (P < 0.001). Although there was
no significant difference in the mean brachial
artery pressure, the pulse pressure, as expected, was greater in the bradyeardic group.
Oxygen consumption of the groups were
similar (fig. 3), and both values were normal
for the age of the subjects.7 10
Atrial pacing was successful in significantly
increasing the HR in six of seven bradyeardic
subjects. One (C.S.) developed second-degree
AV block at a paced rate of 52 beats/min. The
difference in mean paced HR between the
groups was not significant. Atrial pacing
significantly increased the CI of the bradyeardic group, but not in the controls (fig. 1). The
mean paced CI in bradyeardic subjects was
not significantly different from that of the
control group.
The response of the HR, CI, and SI to
muscular exercise is summarized in figure 2.
The CI rose to similar levels in the two
groups. Although the differences between the
groups for HR and SI were not statistically
significant, the bradyeardic subjects tended to
achieve a higher stroke output and lower HR
during exercise than did the control subjects,
findings similar to those at rest. Oxygen
consumption increased comparably in both
T
I*
0
l
0,
-3
'
80
Ge
70-
-9
2.5
60
8
50
7
I1
2t.
1..0
0
40
2.0
--
30
-4
N~~~~~~~~~H ( ET4,MI
72±5 88±1
(60-84) (86-90)
Beats/Minute
45±2 83±4
(41- 51) (69-91)
Figure 1
CI values at rest and during atrial pacing are shown
).
for each control and bradycardic subject (
The mean values are shown by (o) and SEM by
vertical bars. The mean resting HR of the control
subjects was 72 + 5 beats/min (range: 60-84); the
mean HR during atrial pacing was 88 ±+1 beats/min
(range: 86-90). The mean resting HR of the bradycardic group was 45 + 2 beats/min (range: 41-51);
the mean HR during pacing was 83 + 4 beats/mmn
(range: 69-91).
Theresponse of the HR, Sl nd CI to muscular3
20~~~~~~~~~~~~~~~~~~~~~
----
40
80
60
100
120
(
0
HR (BEATS/MIN)
____&d.ycardics
Figure 2
The response of the HR, Si, and CI to muscular
exercise is shown in the control (.--- -e) and brady-
cardic (.---*) subjects. The SI is plotted on the
ordinate and the HR on the abscissa; the isopleths
represent levels of CI. The closed circle to the left
of each connected pair represents resting values and
the closed circle to the right represents exercise values.
Circulation, Volume XLVI, November 1972
SINUS BRADYCARDIA IN THE ELDERLY
927
13
11
9
7
5
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*-
3
*Bradycardic
x-x
200
600
400
Control
800
1000
(cc /minute)
vo2
Figure 3
The relationship between CO and oxygen consumption (VQ2) at rest and during exercise is
) subjects. The symbols (. or x)
shown for the control (X
X) and bradycardic (
on the left represent resting values and those on the right, exercise values. (The slope of each
line is a function of the exercise factor.)
groups during exercise. In addition, the
increases in CO per 100 ml increase in oxygen
consumption (exercise factor) were similar
(fig. 3). The bradycardic group had an
exercise factor of 907 171 ml/ 100 ml and the
60 ml/ 100 ml. The
exercise factors compare closely to those
found by Granath and associates10 in a group
of normal elderly individuals. Figure 3 shows
the relation of oxygen consumption to cardiac
control
group,
885
+
output for all subjects.
The ability of the heart to increase stroke
volume during exercise while maintaining
the HR constant, at a rate just above that
achieved during the previous exercise period,
was evaluated in four bradycardic subjects. As
figure 4 shows, the increase in CI for each of
the subjects was similar to that during the
Circulation, Volume XLVI, November 1972
preceding exercise period, when HR was not
controlled, and resulted almost entirely from
an increase in stroke volume.
With 2.0 mg atropine intravenously, HR
increased significantly in both groups of
subjects (fig. 5). The bradycardic subjects had
a significantly greater absolute and percentage
increase in HR than did the controls
(P < 0.05). Bradycardic subjects tended to
have a more limited HR response during exercise than to atropine when compared to the
control subjects.
Following atropine mean CI did not differ
significantly between the two groups (fig. 5).
A statistically significant increase in mean CI
was found in the bradycardic group (P <
0.001). The difference between the mean
resting CI and postatropine CI in the control
group was not significant.
928
AGRUSS ET AL.
8Or
<-Cs~~~~~~~~~~'I
\
70 -\\
*\ £EAelcise -Pace
60
ATROPINE
Eae,c,se
,
S\\
-5 -
-
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s
W,W, H.
40
-1
FH
-_
*9 B.G.
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6
11
5
-..J
3.0 n
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4
Rest-Pace
BRADYCARDICS
8
7
50
CONTROLS
9
3
20
2
IV'
60
80
'-
100
120
140
HR (BEATS /MIN)
Figure 4
6.
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lines connecting the solid circles show the change
from rest to rest-pace.
The atrioventricular conduction system was
stressed by atrial pacing. Four bradyeardic
subjects developed second-degree AV block at
paced rates of 105 beats/min or less (105, 100,
91 and 52 beats/min, respectively). The
lowest rate at which AV block occurred in the
control subjects was 107 beats/min. Following
sudden cessation of pacing, at the highest rate
attainable, spontaneous sinoatrial activity returned within 1.1 sec (range 0.6-1.1) in each
subject. AV junctional rhythm was not seen in
any subject following the administration of
atropine.
Blood pressure responded normally9' 11 during the Valsalva maneuver in all control and
bradyeardic subjects. All individuals showed a
narrowing of the pulse pressure during phase
II and an overshoot of the BP during phase
IV. The average percentage increase in HR
during the strain (phase II) was similar in
both groups: 27% for controls and 26% for
bradycardic subjects. Slowing of the HR
occurred during phase IV in all subjects, but
in the bradyeardic group the rate usually did
not decrease below the control HR. Following
amyl nitrite inhalation or intravenous meth-
2.5
'311
At the left of the figure the relationship of HR, SI,
and CI is shown in four bradycardic subjects at rest
and during exercise. To the right are plotted the HR,
SI, and CI for these same four subjects during atrial
pacing, while at rest (Rest-Pace) and while exercising
(Exercise-Pace). The solid lines connecting the solid
circles show the change from rest to exercise, and
from rest-pace to rest-exercise. The straight dashed
2.0
72±5 108±12
(60-84) (90-143)
45±2 91±4
(41-51) (70-101)
Beats/ Minute
Figure 5
Cl values at rest and after intravenous administration
of atropine are shown for each control and bradycardic
subject. (*). The mean values are shown
by (o) and SEM by vertical bars. The mean resting
and postatropine heart rates for each group are shown
the bottom of the figure. The range of HR is
at
shown in parentheses.
no significant difference in per cent
of HR change existed between the groups.
Figure 6 shows the response of the HR to
head-up tilt in both groups of subjects. The
control subjects had a significantly greater
percentage increase in HR during tilt (24%)
than did the bradyeardic subjects (11%). The
CI decreased to similar levels in both groups
during tilt. In neither group did the mean BA
pressure change significantly.
oxamine
Discussion
It is known that the resting HR and CO
tend to diminish with age,7 but data relating
to the cardiac performance of asymptomatic
elderly patients with resting heart rates of
40-50 beats/min are lacking. We therefore
studied seven asymptomatic elderly subjects
with sinus bradycardia and compared their
cardiac performance with that of a group of
Circulation, Volume XLVI, November 1972
SINUS BRADYCARDIA IN THE ELDERLY
TILT
100
r
90
80 F
-1.1
qll.14
-1.
c 70
t
q)
11.
60
50
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40
30
Supine
Tilt
Figure 6
The HR at rest and during head-up tilt is shown for
each control (---a-) and bradycardic (
)
subject. The means at rest and during tilt are shown
by (o) and SEM by vertical bars, and are connected
by the heavy line.
age-matched control subjects. Although we
found bradyeardic subjects to differ from
normal in several respects, they had normal
cardiac performance at rest and during
exercise, and had no evidence of autonomic
nervous system dysfunction.
Although both groups achieved similar
levels of CO during exercise the bradyeardics tended to do so by means of a higher
stroke output and lower HR. This is similar to
the resting hemodynamic pattern of the
bradyeardics wherein they maintained a normal CO by an increased stroke output. With
the HR held constant during exercise in four
of the bradyeardic subjects it was found that
levels of CO could be achieved that were
similar to those attained when the HR was
allowed to change. This ability to vary left
ventricular stroke output in order to maintain
a normal CO during stress tends to be lacking
in patients with chronic heart disease.'2
Following the administration of atropine,
bradyeardic subjects had a much greater
Circulation, Volume XLVI, November 1972
929
absolute and percentage increase in HR. This
would suggest that increased vagal tone13 was
an important factor in the slow heart rates in
the bradyeardic subjects. It is possible that
had the exercise stress been greater the
bradycardic subjects would have achieved
heart rates similar to the controls, since
withdrawal of vagal tone accounts in part for
the increase in HR during exercise.14
Most studies 15, 16 have shown no signfficant
change in CO with either atrial pacing or
atropine in normal subjects. Despite apparently normal cardiac function in all subjects, we
found that CO increased significantly only in
bradyeardic subjects when HR was increased
by atrial pacing or atropine. The explanation
for this finding is not clear. It would be of
interest to study the CO response to these
interventions in bradyeardic athletes.
Several significant similarities existed between the bradyeardic and control groups.
The resting and exercise cardiac outputs of the
two groups were similar. Both groups of subjects had similar increases in CO per 100 ml
increase in oxygen consumption, the exercise
factor. The resting cardiac outputs were
normal for the age of the subjects.7 The
exercise cardiac outputs and exercise factors
were in agreement with the values that
Granath and his associates found in a group of
similarly aged normal men performing supine
bicycle exercise.10 It is thus concluded that
normal cardiac performance was present in
our group of bradyeardic subjects.
By the tests described in this study, no
evidence of autonomic nervous system dysfunction was found in any subject. The normal
responses of the BP and HR to the Valsalva
maneuver and of the HR to manipulation of
the BP suggests that an intact baroreceptor
reflex arc was present and that sympathetic
and parasympathetic pathways were also
intact.17 In addition, none of the bradyeardic
subjects had clinical evidence of generalized
dysfunction of the sympathetic nervous system, e.g. orthostatic hypotension, diminished
sweating, or pupillary changes. Although all
subjects had an increase in HR during headup tilt, the response of the HR in the
930
AGRUSS ET AL.
bradyeardic subjects was significantly less
than that of the control subjects. A diminished increase in HR during head-up tilt can
be seen in patients who are in congestive heart
failure."' 19 However, none of the bradycardic
subjects had any evidence of impaired cardiac
performance. It is possible that an increased
level of vagal tone accounted for the blunted
HR response to tilt in the bradyeardic
subjects.
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Although a significant number of our
bradycardic subjects had evidence of impaired
AV conduction, this was the only evidence
suggestive of cardiac disease. Unlike the
findings in patients with so called "sick sinus
node" disease, serial electrocardiograms
showed normal sinus node activity, the
recovery time of sinoatrial discharge following
atrial pacing was normal, and our studies
showed normal left ventricular performance.
Because of the patient's age, however, coronary artery disease or degenerative disease in
the SA node or atrial muscle must be
considered. Only by long term followup of
these asymptomatic bradyeardic subjects will
we learn whether their bradycardia will
remain benign. There is a need for comparable studies in a symptomatic group of subjects
with sinus bradyeardia, especially with regard
to the effects of atrial pacing, exercise and
atropine.
As shown in this report, significant degrees
of sinus bradyeardia may be associated with
aging. In this latter setting, increased vagal
tone may be a significant contributing factor
to the bradyeardia, and more importantly,
normal cardiac performance can be present.
Therefore, the implications and management
of sinus bradycardia depend upon the setting
in which it occurs.
3. RASMUSSEN K: Chronic sinoatrial heart block.
Amer Heart J 81: 38, 1971
4. FERRER MI: The sick sinus syndrome in atrial
disease. JAMA 206: 645, 1968
5. SCHUILMAN CL, RUBENSTEIN JJ, YURCHAK PM,
DESANCTIs RW: The `sick sinus" syndrome:
Clinical spectrum. (Abstr) Circulation 42
(suppl III): III-42, 1970
6. FRUEHAN CT, OBEID AI, SMULYAN H, EIcH RH:
Sick sinus syndrome: One year's experience.
(Abstr) Circulation 42 (suppl III): III-154,
1970
7. BRANDFONBREN-ER M, LANDOWNE M, SHOCK NW:
Changes in cardiac output with age. Circulation 12: 557, 1955
8. ADOLPH RJ, HOLMES JC, FUKUSUMI H: Hemodynamic studies in patients with chronically
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Circulation, Volume XLVI, November 1972
Significance of Chronic Sinus Bradycardia in Elderly People
NEIL S. AGRUSS, ELAINE Y. ROSIN, ROBERT J. ADOLPH and NOBLE O.
FOWLER
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Circulation. 1972;46:924-930
doi: 10.1161/01.CIR.46.5.924
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX
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