Left Ventricular Systolic Time Intervals as
Indices of Postural Circulatory
Stress in Man
By R. W. STAFFORD, M. D., W. S. HARmS, M.D.,
AND
A. M. WEISSLER, M.D.
SUMMARY
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The effects of graded increments of passive head-up tilt on the duration of the
systolic time intervals corrected for heart rate were investigated in 15 normal subjects.
Head-up tilt caused a prolongation of the pre-ejection period and a shortening of the
left ventricular ejection time, while total electromechanical systole diminished minimally.
The lengthening of the pre-ejection period and abbreviation of the left ventricular
ejection time increased progressively with stepwise increments of head-up tilt. The
application of venous occlusive toumiquets produced changes in the systolic intervals
directionally similar to those observed with head-up tilt. In contrast to the normal
subjects, three patients with congestive heart failure demonstrated no change in the
systolic time intervals during head-up tilt. After diuresis in two of the patients with
heart failure, the responses of their systolic time intervals to head-up tilt retumed
toward normal.
Additional Indexing Words:
Electromechanical systole
Head-up tilt
effects of graded increments of head-up tilt on
heart rate, arterial pressure, and the time
intervals of left ventricular systole. In addition, the circulatory changes produced by
head-up tilt were compared with those
resulting from the application of venous
occlusive tourniquets.
THE ONLY noninvasive measurements
that are currently used to characterize
gravitational circulatory stress in man are
heart rate and arterial pressure. Previous
studies in norrnal subjects and patients with
heart disease have shown that changes in the
systolic time intervals reflect, in a convenient
and sensitive manner, alterations in left
ventricular performance.l1 To test the possible usefulness of these atraumatic measurements in assessing left ventricular responses to
gravity, the present studies were performed in
normal subjects and in patients with heart
failure. These studies have delineated the
Methods
As described previously,14 the systolic time
intervals were measured from simultaneous, fastspeed (100 mm per second) recordings of the
electrocardiogram, phonocardiogram, and carotid
arterial pulse tracing. Total electromechanical
systole (QS2) was measured from the onset of
ventricular depolarization to the initial high
frequency vibrations of the second heart sound.
The left ventricular ejection time (LVET) was
measured from the onset of the carotid upstroke
to the trough of its incisura. The left ventricular
pre-ejection period (PEP) was derived by
subtracting the left ventricular ejection time from
total electromechanical systole. The intervals were
calculated as the mean of measurements of at
least 10 consecutive beats, each read to the
nearest 5 msec. When sinus arrhythmia caused
heart rate to vary more than 10 beats per minute,
20 consecutive beats were analyzed. Heart rate
From the Department of Medicine, Ohio State
University College of Medicine, Columbus, Ohio.
Supported in part by U. S. Public Health Service
Grants HE-5546, HE-5786, HE-06737, Career Program Award HE-13971, and a grant from the
Central Ohio Heart Association.
Requests for reprints: Arnold M. Weissler, M.D.,
Department of Medicine, Ohio State University- Hospital, 410 West 10th Avenue, Columbus, Ohio 43210.
Received September 15, 1969; accepted for publication November 19, 1969.
Circulaiion, Volume XLJ, March 1970
Left ventricular ejection time
485
STAFFORD ET AL.
486
PHONo
AORTIC
PRESSURE
LV PRESSURE
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EGG
Figure 1
Relation of the measured systolic time inntervals to the
cardiac cycle.
(HR) was determined by dividing th e average RR interval into 60. Figure 1 shows sichematically
the relation of the measured systolic tiime intervals
to the cardiac cycle.
Total electromechanical systole a;Lnd the left
ventricular ejection time are inverselIy related to
heart rate; the pre-ejection period iis minimally
affected by heart rate. The followin g regression
equations,5 derived from data previou sly obtained
in 211 normal subjects, were used to) correct the
systolic time intervals in millisecon is for heart
rate.
Systolic
interval
QS2 (msec)
Sex
Regression equation
QS2 = 2.1 EIR + 546
F QS2 = 2.0I IR + 549
LVET (msec) M LVET
1.'7 HR + 413
F LVET =- Lf6 HR + 418
M
PEP (msec)
PEP= -0.41HR + 131
F PEP = 0.4 ]HR + 133
Deviations from these normal data were
calculated as the difference between t observed
interval and that predicted for heart r*ate from the
normal regression equation. The diffe*rence in the
deviations from the normal regressi'on equation
before and after tilt represents the tilt response
and is expressed as AQS2, APEP, aLnd ALVET.
These values were calculated by sut tracting the
deviations from the normal regressiion equation
after tilt from the immediately prece-ding supine
control deviation from normal. The ratio of the
pre-ejection period to left ventricuilar ejection
M
-
-
--
,he
time (PEP/LVET) was determined directly from
the values uncorrected for heart rate. Arterial
pressure was measured with a cuff sphygmomanometer. Statistical analysis was performed by the
methods of Snedecor.6
Normal volunteers, eight men and seven
women, all active students, house staff, or
laboratory technicians of average age 23 years,
(range 18 to 28 years) were studied. Tilting was
accomplished by use of an electrically powered
tilt table. The systolic time intervals, heart rate,
and arterial pressure were measured in each
subject in the supine position, and at 2}2, 5, 10, 15,
20, .25, 30, 45, 60, and 90 degrees of passive
head-up tilt. This sequence in head-up tilt was
followed in all studies. Before each of the 10
applications of head-up tilt, supine control
determinations of the time intervals, heart rate,
and arterial pressure were obtained. The changes
observed with each application of head-up tilt
were calculated from the immediately preceding
supine measurement. In preliminary studies it
was determined that steady-state responses in
heart rate, systolic intervals, and arterial pressure
were achieved in from 3 to 15 minutes of head-up
tilt. Control supine levels returned within 4
minutes after return to the horizontal position.
Arterial pressure was determined during the
fourth minute, and the systolic time intervals
were recorded during the sixth minute of head-up
tilt. Arterial pressure was then measured during
the fourth minute, and the systolic time intervals
were recorded during the sixth minute after the
subject was returned to the supine position. There
was no significant variation in pre-tilt supine
control levels throughout the studies.
To determine the effects of venous pooling
produced by nongravitational means, venous
occlusive cuffs were applied to the arms and
thighs of five normal men. The cuff pressures
were kept 10 mm Hg below the arterial diastolic
pressure. The systolic time intervals were recorded during the sixth minute of venous
occlusion.
Three patients with severe congestive heart
failure (New York Heart Association Classification III in each) due to primary myocardial
disease in two and hypertensive and arteriosclerotic heart disease in one, were studied. Arterial
pressure, heart rate, and the systolic time
intervals were measured at 0, 30, 60, and 90
degrees of head-up tilt. After diuresis and clinical
recovery from heart failure, these studies were
repeated in two of the patients. Each of these
patients lost 15 pounds of body weight between
the studies.
The hydrostatic effect of head-up tilt is a
function of the sine of the angle of tilt.7 For this
reason, the changes in the systolic time intervals
Circulation, Volume XLIl, March 1970
A487
LV SYSTOLIC TIME INTERVALS
with head-up tilt were plotted against the sine of
the angle of tilt in figures 2 and 3. For
comparison, these figures also include the absolute angle of tilt.
Results
Head-up Tilt
The effects of head-up tilt on the systolic
time intervals, heart rate, and arterial pressure
in the 15 normal subjects are summarized in
table 1 and in figure 2. These effects were
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determined by subtracting the value observed
at each level of tilt from the immediately
preceding control observation obtained in the
supine position. The supine control determinations did not change significantly during the
course of the study.
Head-up tilt increased the heart rate,
shortened total electromechanical systole and
the left ventricular ejection time, and prolonged the pre-ejection period. When corrected for increase in heart rate (fig. 2), there
was minimal shortening of electromechanical
systole (AQS2), accompanied by considerable
shortening of left ventricular ejection (A
LVET) and prolongation of the pre-ejection
period (APEP). These changes were significant beyond 10 degrees of head-up tilt. The
ratio of the pre-ejection period to the left
ventricular ejection time (PEP/LVET) increased significantly with tilt of 20 degrees or
greater. In contrast to the systolic arterial
pressure, which failed to change significantly,
Table 1
Effects of Head-up Tilt on Systolic Time Intervals in 15 Normal Subjects*
Angle of
tilt
Supine
BR
66
50
200
300
450
600
900
PEP
(msec)
APEP
(msec)
-1
299
-1
109
0
(±9)
(±1)
(±7)
(±1)
(±4)
(±1)
63
410
(±8)
-2
(±1)
-4
-6
(±1)
-9
(±2)
-15
i11
(±3)
(±1)
-6
300
(±7)
295
(i7)
289
4
(±1)
5
(+2)
9
(+1)
14
(i2)
64
PEP/
LVET
300
108
0.36
(±7)
(±4)
(+0.1)
64
408
(±9)
406
(±4)
(±9)
(±1)
(±7)
(±2)
(±4)
64
404
(i8)
-7
281
-21
124
(±1)
(±7)
(±2)
(±4)
(±4)
25°
ALVET
(msec)
65
(±4)
15°
-
LVET
(msec)
(±4)
(±4)
10°
AQS2
(mBec)
408
(+8)
408
(±4)
2.50
QS2
(msec)
114
(±4)
117
SAP
DAP
(mm Hg) (mm Hg)
0.37
115
(+2)
113
67
(i2)
66
(±0.01)
(±2)
(i2)
0.37
(+0.01)
0.39
113
(±2)
113
(±0.01)
(±2)
0.40
113
67
(i2)
66
(±1)
70
(±0.02)
(±2)
(±1)
0.44
112
72
(±0.02)
(±2)
(±2)
67
399
-3
273
-23
126
19
0.47
113
75
(±4)
(±+9)
(±2)
(±8)
(±2)
(±4)
(±2)
(±40.02)
(±2)
(±1)
69
397
-5
268
-25
128
21
0.48
112
75
(i4)
(±9)
(±1)
(±7)
(i2)
(i2)
(±2)
(±0.02)
(i2)
(i2)
76
379
-8
247
-34
132
28
0.54
113
78
(±4)
(±9)
(±2)
(±8)
(±3)
(±4)
(±2)
(±0.02)
(±2)
(±2)
82
366
-6
233
-38
134
32
0.58
112
81
(±5)
(+9)
(±2)
(±7)
(±2)
(±t4)
(±2)
(±0.02)
(±2)
(±3)
85
360
-7
227
-41
134
34
0.59
110
83
(±4)
(±9)
(±3)
(±7)
(±2)
(±5)
(±2)
(±0.02)
(±3)
(+3)
* Data represent mean values plus standard error of the mean in parentheses.
The values for the systolic time intervals (QS2, LVET, and PEP) and the ratio PEP/LVET are uncorrected for
heart rate. The changes (A) in the systolic time intervals with head-up tilt were determined by subtracting the
deviation from the normal regression equation after tilt from the immediately preceding supine control deviation
from normal.
Abbreviations: HR = heart rate, QS2 = QS2interval, LVET = left ventricular ejection time, PEP = pre-ejection
period, SAP = systolic arterial pressure, DAP = diastolic arterial pressure.
Csrcu1ation, Volume XLI, Marcb 1970
STAFFORD ET AL.
488
+40-
+20-
APEP
meec.
0-
~~~~~AQS2
X
-20CHANGE
FROM
CONTROL
APEP
-401
CHANGE
FROM
CONTROL
A QS2
ALVET
ALVET
+20-
AHR
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beats/min.
I-SE
0
Figure 3
ANGLE OF TILT
3Q0
450
I50
90f
a
0
.2
.4
SINE ANGLE
.6
.8
LO
TILT
Figure 2
Mean changes in the systolic time intervals and heart
produced by head-up tilt in 15 normal subjects.
The values for the systolic time intervair represent
difference in deviation from the normal regression
equation for heart rate before and after tilt. Above 15
degrees of head-up tilt, all changes in the systolic time intervals were significant (APEP, ALVET,
P < 0.001, AQS2 <0.05). Heart rate changes were
significant beyond 25 degrees (P < 0.001).
rate
diastolic arterial pressure increased significantly above the control value at all angles of tilt
above 10 degrees (P < 0.01).
Effect of venous occlusive tourniquets on total electromechanical systole (AQS2), the left ventricular ejection
time (ALVET), and the pre-ejection period (APEP) in
five normal supine male subjects. Each line represents
the difference in deviation from the normal regression
equation before and after application of venous occlusive tourniquets. The bars represent the standard
error of the mean response.
MEAN
(n.15)
HEART FAILURE
A
msec. +
CHANGE
FROM
CONTROL
A LVET
APEP
B
Venous Occlusive Cuffs
In five normal supine male subjects, the
application of venous occlusive tourniquets
increased the heart rate from 54 (SE 6.8) to
61 (SE 8.5) beats per minute. Total electromechanical systole and the left ventricular
ejection time diminished and the pre-ejection
period lengthened. When corrected for the
increase in heart rate, the ejection time
shortened by 16 msec and the pre-ejection
period lengthened by 14 msec, while electromechanical systole shortened by 3 msec
(fig. 3).
msec.
OT
0
401
-
A PEP
.4
O
.8
SINE ANGLE
N
A-LVET
.4
OF TILT
Figure 4
A. Effect of head-up tilt on the left ventricular preejection period and ejection time in 15 normal subjects
and in three patients with severe congestive heart
failure. B. Effect of head-up tilt on the left ventricular
pre-ejection period and ejection time in 15 normal
subjects and in two patients restudied after diuresis.
Heart Failure
In three patients with severe congestive
heart failure, head-up tilt produced only
minimal changes in the systolic time intervals,
heart rate, and arterial pressure. After diuresis
circulation, Volume XLI, Marcb 1970
LV SYSTOLIC TIME INTERVALS
in two of the patients, there was a return
toward normal in the response of the systolic
time intervals to head-up tilt (fig. 4).
Discussion
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Previous investigations have defined the
hemodynamic consequences of assuming the
upright posture in man. By causing the venous
pooling of blood below the heart,7 10 the
gravitational stress incurred by head-up tilt
diminishes ventricular filling, end-diastolic
volume, stroke volume, and cardiac
output.1 -20 Owing to baroreceptor-mediated
reflexes, mean arterial pressure increases
slightly and peripheral resistance and heart
rate rise significantly.'9
The present results have demonstrated a
quantitative relation between postural gravitational stress, expressed as the sine of the angle
of head-up tilt, and the systolic time intervals
corrected for heart rate. Earlier, Lombard and
Cope2' showed that the left ventricular
ejection time shortens when normal subjects
sit or stand up. Raab and associates22 reported
that standing up shortens total electromechanical systole and the left ventricular ejection
time and prolongs the pre-ejection period. In
neither of these two previous studies were the
systolic time intervals corrected for the effects
of heart rate, nor were graded increments of
head-up tilt observed.
The changes observed in the systolic
intervals with increasing degrees of head-up
tilt parallel closely the hemodynamic changes
with increasing tilt reported previously by
Tuckman and Shillingford.19 In normal subjects these authors observed that cardiac output fell maximally at 30 degrees head-up tilt,
failing to decrease further with greater
tilt, although stroke volume fell at all angles
of tilt through 60 degrees. Consonant with the
data of these authors on stroke volume, the
effects of gravity on the pre-ejection and
ejection periods tended to continue with headup tilt to 60 degrees. At 90 degrees head-up
tilt, the changes in the systolic intervals were
only slightly greater than at 60 degrees headup tilt.
In studies of animals and man,1 23-25
reductions of ventricular filling and stroke
Circulation, Volume XLI, March 1970
489
volume have been shown to prolong the preejection period and shorten the duration of
left ventricular ejection. During head-up tilt,
the pattern of changes that occurs in the
systolic time intervals most likely reflects the
decreases of ventricular end-diastolic and
stroke volume consequent to venous pooling.
Probably operating through similar mechanisms, the application of venous occlusive
tourniquets, which reduces stroke volume and
cardiac output without significantly altering
diastolic arterial pressure,'8' 26, 27 also prolongs
the pre-ejection period and shortens the left
ventricular ejection time. The effects of this
nongravitational stress on the systolic time
intervals resemble those found with 15 to 20
degrees head-up tilt and approach 40% of that
observed with 90 degrees head-up tilt.
Associated with the diminished left ventricular end-diastolic volume, other hemodynamic
factors may contribute to the effects of gravity
upon the pre-ejection and ejection periods in
normal subjects. By increasing the isovolumic
pressure gradient, either a fall in left ventricular end-diastolic pressure or a rise in aortic
diastolic pressure would tend to lengthen the
pre-ejection period. The magnitude of the
effect of a fall in left ventricular end-diastolic
pressure per se cannot be assessed from the
present results. However, in view of the
relatively minor influence of peripheral venous
pooling on left ventricular end-diastolic pressure in normal subjects,28 this would appear to
be slight. Head-up tilt is responsible for the
initiation of compensatory baroreceptor mediated reflex activity with a consequent increase
in sympathetic cardiostimulatory activity and
peripheral vasoconstriction.29 These changes
of themselves might alter the systolic intervals.
Sympathetic stimulation of the myocardium
would tend to shorten the pre-ejection period
by accelerating the isovolumic rise of left
ventricular pressure.3 30 When other variables
are kept constant, acutely induced increases in
peripheral resistance would tend to prolong
the left ventricular ejection time.31 Despite the
presence of these effects during head-up tilt,
the pre-ejection period actually lengthened
while the ejection time was abbreviated.
AO0
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These reflex effects, hence, cannot explain the
observed changes in systolic intervals with
head-up tilt.
Patients with congestive heart failure who
are studied in the supine position have systolic
time intervals resembling those observed in
normal subjects during head-up tilt: a long
pre-ejection period, short left ventricular
ejection time, and little change in total
electromechanical systole.4'5 In heart failure
the long pre-ejection period and short ejection
time are well correlated with the reduced
stroke volume and cardiac output.4' 5 The two
groups, patients in heart failure and normal
subjects in the upright posture, differ markedly in their left ventricular end-diastolic volumes. These are large in patients with left
ventricular failure32 and small in normal
subjects undergoing upright tilt.20 Both in the
supine patients with left ventricular failure
and normal subjects during head-up tilt, the
long pre-ejection period probably reflects a
slower rise of left ventricular pressure during
isovolumic contraction. In heart failure, it is
the depressed myocardial function33 34 that
slows the rise of isovolumic pressure. In
normal subjects during tilt, myocardial function is unimpaired, and it is the reduction in
left ventricular end-diastolic volume and
myocardial fiber length that most probably
results in the slower rise of isovolumic
pressure.35 36 In both groups of subjects the
shorter ejection time is associated with a
reduction in stroke volume. The mechanism of
shortening in the ejection time may be viewed
in several ways. The shortened ejection time
may simply reflect the reduction of stroke
volume caused by either depressed ventricular
function in heart failure or diminished enddiastolic volume during head-up tilt in normal
subjects. On the other hand, the delay in
aortic valve opening caused by the slower
isovolumic rise of left ventricular pressure, at
a time when total systole fails to lengthen, can
explain the diminished duration of ejection in
both heart failure and during head-up tilt.
When considered relative to the contractile
properties of the myocardium, it is probable
that in both hemodynamic states (heart
STAFFORD ET AL.
failure and head-up tilt) the stroke volume
and systolic temporal responses are but
differing hemodynamic reflections of a common dynamic change in the myocardium, that
of a decreased rate of developed force or
myocardial contraction, or both, during the
pre-ejection and ejection phases of the cardiac
cycle. These changes are the result of
depressed cardiac function in heart failure and
diminished end-diastolic fiber length in the
upright posture.
In our three patients with severe heart
failure, head-up tilt failed to change the
systolic time intervals, heart rate, or arterial
pressure. This absence of postural responses is
consistent with previous demonstrations that
during upright tilt patients with heart failure
or pulmonary congestion due to mitral valve
disease fail to lower their right ventricular
end-diastolic volume, cardiac output, and
stroke volume.'1' 37,38 The inability of upright
tilt to alter the systolic time intervals in
patients with congestive failure may, in part,
reflect the antigravitational effects of hypervolemia, elevated tissue pressure, and increased venomotor tone. By minimizing the
shift of blood away from the central circulation, these extracardiac concomitants of heart
failure may prevent the usual hemodynamic
effects of gravitational stress. In support of
this hypothesis is the observation that diuresis
restored the responsiveness to head-up tilt in
two of the patients with heart failure.
Current aerospace and deep-sea explorations have heightened the need to develop
practical and effective noninvasive methods
for monitoring circulatory changes in man. In
the present study, the gravitational stress
induced by head-up tilt was clearly shown to
affect left ventricular performance. The measurement of the systolic time intervals would
appear to provide a convenient, sensitive, and
reliable method for rapidly assessing such
gravitational effects upon the human circulation.
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Circulatioi, Volxme XUl, Mcrcb 1970
Left Ventricular Systolic Time Intervals as Indices of Postural Circulatory Stress
in Man
R. W. STAFFORD, W. S. HARRIS and A. M. WEISSLER
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Circulation. 1970;41:485-492
doi: 10.1161/01.CIR.41.3.485
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