Download Reversible Cardiac Failure During Angina Pectoris

Reversible Cardiac Failure
During Angina Pectoris
Hemodynamic Effects of Atrial Pacing
in Coronary Artery Disease
By JOHN
0.
PARKER, M.D., J. RODNEY LEDWICH, M.B.,
ROXROY 0. WEST, M.D.,
AND
ROBERT B. CASE, M.D.
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SUMMARY
Left ventricular end-diastolic pressure and left ventricular stroke work were measured
during a 10-min period of atrial pacing in 10 nolral subjects and 30 patients with
coronary artery disease. The normal subjects and the patients with coronary artery
disease who did not experience angina during pacing reacted similarly with a fall in
left ventricular end-diastolic pressure from 8 to 2 mm Hg returning to control values
on cessation of pacing. The average left ventricular end-diastolic pressure during pacing
in the 21 patients who developed angina was similar to control values although this
pressure rose to abnormal levels in four patients. On cessation of pacing the left
ventricular end-diastolic pressure rose abruptly to an average value of 22 mm Hg.
This lack of elevation of filling pressure during pacing and the rise to abnormal levels
on termination of pacing can best be explained by relating left ventricular end-diastolic
pressure to left ventricular stroke work. Analyzed in this fashion it is evident that the
ischemic ventricle is operating on a depressed ventricle function curve. This depression
of function is reversible following cessation of pacing and can be prevented by the prior
administration of nitroglycerin.
Additional Indexing Words:
Ventricular function curve
Left ventricular stroke work
Left ventricular end-diastolic pressure
Nitroglycerin
Hg.5' I,9 This was not accompanied by an
ANGINA PECTORIS, precipitated by
exercise or occurring spontaneously, is
generally, but not always, associated with an
elevation of left ventricular filling pressure.'-1
Our investigations have consistently shown a
high left ventricular end-diastolic pressure
during exertional angina, averaging 34 mm
increase in left ventricular stroke work and we
have interpreted these changes as evidence of
left ventricular failure during myocardial
ischemia. Recent reports8' 12-17 have shownl
that angina can be readily produced by
increasing heart rate with atrial pacing,
although angina produced in this manner is
associated with normal or only slightly
elevated left ventricular filling pressure.8' 12
This is in sharp contrast to the gross
abnormalities observed during exertional or
spontaneous angina. In view of this seeming
paradox, we have assessed left ventricular
performance during myocardial ischemia
utilizing the technic of right atrial pacing. The
effect of nitroglycerin on the clinical and
From the Department of Medicine, Queen's
University and Kingston General Hospital, Kingston,
Ontario.
Work was supported in part by Ontario Heart
Foundation (2-13) and the Medical Research Council
of Canada (MA-3062). Work was done during Dr.
Case's appointment as a visiting scientist by the
Medical Research Council of Canada.
Address the reprints: Dr. John 0. Parker,
Cardiopulmonary Laboratory, Etherington Hall,
Queen's University, Kingston, Ontario, Canada.
Circulation, Volume XXXIX, June 1969
745
PARKER ET AL.
746
hemodynamic consequences of pacing was
also evaluated. The precipitation of angina
solely by increase in heart rate also makes it
possible to examine left ventricular function
without the changes in cardiac output, oxygen
consumption, and circulating catecholamines
that accompany exercise.
Methods
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Hemodvnamic investigations with subsequent
selective cine-coronary arteriography and left
ventriculography were performed in 42 patients
with known or suspected coronary artery disease
without cardiomegaly, arrhythmias, or clinical
evidence of cardiac failure. None of the patients
was receiving digitalis or diuretics at the time of
the study. Ten patients had systolic pressure
exceeding 140 mm Hg, in two of whom it exceeded 170, but only four had diastolic pressure
exceeding 90 mm Hg. None had been treated for
arterial hypertension or exhibited hypertensive
retinopathy exceeding grade 1 in severity.
The patients were brought to the laboratory the
day prior to the study so they would be familiar
with the surroundings and the nature of the
procedure. Resting minute ventilation was
recorded and a period of supine leg exercise
carried out on a bicycle ergometer. This allowed
us to observe the patient's response to stress and
to estimate the pacing rate that would be
required to produce angina. In general, the heart
rate required to produce pain with atrial pacing
was 20 beats/min more than that coincident with
the onset of angina during exercise.
Patients were studied in the fasting state
without premedication. Under local anesthesia
the brachial artery and two veins were isolated in
the right antecubital fossa. The tip of a no. 6
bipolar pacing catheter was placed either in the
midportion of the coronary sinus or against the
lateral wall of the right atrium. A no. 9 double
lumen Cournand catheter was passed into the
right heart so the tip lay in the pulmonary artery
and the proximal lumen in the right ventricle. A
no. 8 Sones catheter was inserted into the left
ventricle from the right brachial artery and the
left brachial artery was cannulated with a
Cournand needle. Lead II of the electrocardiogram and pressures from the pulmonary artery,
right ventricle, brachial artery, and left ventricle
were recorded at 5-min intervals during a 15-min
control period (control I). The cardiac output
was measured in duplicate during the final 3 min
by the dye-dilution technic using indocyanine
green. A 9 to 10-min period of pacing was then
carried out during which the electrocardiogram
and pressures were measured during the first,
fourth, sixth, and ninth minutes. The cardiac
output determination was repeated during the
final 3 min of pacing. Oxygen consumption was
measured and brachial and pulmonary arterial
blood withdrawn for analysis of pH, P02, PCO2,
and oxygen saturation, with both cardiac output
determinations. Continuous recordings of brachial
artery and left ventricular pressures were made
during the termination of pacing. In later studies,
pacing was interrupted for 15 sec at 2-min
intervals to determine the effect of sudden
reduction in heart rate.
Twenty minutes after pacing was terminated
hemodynamic measurements, including the cardiac output (control II) were made in 20 patients.
Following this a 0.5-mg tablet of nitroglycerin in
a lactose base (glyceryl trinitrate*) was chewed,
and these parameters were measured again
between the sixth and tenth minute following
drug administration (control NG), and then a
second period of pacing was carried out at a rate
identical to that of the first study.
Pressures were measured with P 23Db Statham
strain gauges from a zero reference level 5 cm
below the angle of Louis and were recorded on a
photographic recorder.t Pressures were measured
over at least two respiratory cycles and the mean
pressures in the brachial and pulmonary arteries
were obtained electronically. Recording speed
was normally 25 mm/sec, but for determination
of ventricular end-diastolic pressure a high
sensitivity was employed with a speed of 100
mm/sec. Expired air was collected in a Tissot
spirometer and analyzed for carbon dioxide and
oxygen by the micro-Scholander technic.
The left ventricular stroke work index in gM/M2 was calculated using the formula:
LVSWI = SI x (BAm -LVEDP)
X
13.6
where SI = stroke index in mI/M2; BAm = brachial artery mean pressure in mm Hg, and
LVEDP= left ventricular end-diastolic pressure
in mm Hg. A modified tension-time index was
calculated as the product of peak left ventricular
systolic pressure and heart rate. This modification
is based on the fact that peak systolic pressure
is a more important determinant of myocardial
oxygen consumption than the total area under the
left ventricular systolic pressure curve.18 The
maximum rate of rise of left ventricular
pressure (dp/dt) was obtained by an electronic
differentiator.t There are theoretical objections to
measurement of dp/ dt using a fluid-filled catheter
and external transducer but direct in vivo
*Burroughs Wellcome & Co. (Canada) Ltd.
tElectronics for Medicine DR8 Recorder, White
Plains, New York.
:Electronics for Medicine, White Plains, New York.
Circulation, Volume XXXIX, June 1969
CARDIAC FAILURE DURING ANGINA PECTORIS
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comparison with a catheter tip transducer at
rates of 75 to 150/min has shown that the two
methods of measurement correspond closely up to
a value of 2,000 mm Hg/sec." The pH, pCO2,
and P02 were measured on a pH/gas analyzer*
and the oxygen saturation measured with a
hemoreflector.t
Following the completion of these hemodynamic studies, selective cine-coronary arteriography and left ventriculography were carried out
in all patients. Twelve patients were found to
have normal coronary arteriograms and left
ventriculograms and had no hemodynamic or
electrocardiographic evidence of heart disease
and were placed in the normal group. The
remaining 30 patients had major obstructive
lesions in one or more coronary vessels. The left
ventriculograms show minor local impairment of
contractility in some patients, but none had
evidence of ventricular aneurysm.
Results
747
coronary artery disease developed angina
during the period of atrial pacing. This
developed within 1 to 5 min and persisted,
usually with increasing severity, until pacing
was terminated at the end of 9 to 10 min. In
no case was it necessary to discontinue pacing
prematurely. After pacing was terminated,
pain frequently stopped within 30 sec, was
generally absent by 2 min, but in the
occasional patient pain subsided slowly over a
5 to 6-min period. For purposes of analysis,
three groups will be considered: (a) angina
group-21 patients with coronary artery
disease who developed pain with pacing, (b)
non-angina group-nine patients with coronary artery disease who did not experience
pain with pacing, (c) normal group-12
patients free of cardiac disease.
Twenty-one of the 30 patients with
LVEDP
mmHg
25r
*Instrumentation Laboratories, Inc.
tAmerican Optical Co.
LVSWI
GM-M/M2
-ANGINA
- - - NON-ANGINA
NORMAL
p
-_
-
50 F
"S~
40 F
ANGINA
rillWill
--NON ANGINA
NORMAL
Is\s,4N
\<
"s
-
30 F
//
4\
-
4
/I /
20F
1O
CONTROL
PACING
PACING STOPPED
Figure 2
PACING
CONTROL
Figure
1
Left ventricular stroke work index (LVS-WI) showing
decrease in each of the three groups of patients
during the pacing period.
a
Circulation, Volume XXXIX, June 1969
Left ventricular end-diastolic pressure (LVEDP) in
the three groups of patients before and during pacing,
and in the immediate post-pacing period. The LVEDP
falls during pacing in the normal and non-angina
groups but shows little change in the angina patients.
In the post-pacing period it returns to control in the
normal and non-angina group but rises to abnormal
levels in the angina patients.
748
748
PARKER ET AL.
Table 1
Summary of Hemodynamic Effects of Atrial Pacing
BAm
(mm Hg)
LVEDP
(mm Hg)
PAm
(mm Hg)
V02
(ml/min/m2)
HR
(beats/min)
CI
(L/min/m2)
SI
(mI/M2)
SERI
(ml/sec/m2)
LVSWI
(g-m/m2)
Angina group (n = 21)
Control
101 i 14.5 8.0 z3.2 12.7 ±2.7 137 i 13.5 78 i 12.3 2.92 ± 0.55 38 i 7.0 116 i 19.3 47.2 4 8.6
Pace
119 ±22.7 9.2 +6.0 20.1 ±7.5 160 ±22.5 144 i 10.9 3.03 ±0.88 21 i6.9 83 421.3 32.7 ±t 11.6
Post-pace
21.6 i 6.7
Non-angina group (n
Control
95 ± 4.9
Pace
102 i 8.7
Post-pace
Normal group (n
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Control
Pace
Post-pace
90 ±4 11.0
93 ± 11.5
=
9)
9.5 ± 2.9 12.3 ± 1.7 147 ± 23.1 79 4 16.5 3.03 4 0.22 40 ± 5.9 126 i 15.7 46.7 t 8.7
3.2 ± 2.2 13.6 ± 2.7 153 ± 17.4 140 ±6.8 3.18 ± 0.42 23 4 3.8 91 i 11.5 31.2 ± 6.3
12.7 i 2.9
=
12)
8.7 ± 2.6 11.8 ± 2.2 130 ± 21.3 72 ± 10.2 2.87 ±0.41 40 ± 5.1 121 ± 14.1 44.9 ± 10.1
2.3 1.9 14.5 i 2.0 143 i 22.8 142 ± 6.0 3.11 ±0.71 22 ± 5.0 88 ± 23.0 26.8 ± 7.0
9.8 ± 2.8
Abbreviations: control = sinus rhythm; pace = atrial pacing; post-pace = immediately following pacing; BAm =
brachial artery mean pressure; LVEDP = left ventricular end-diastolic pressure; PAm = pulmonary artery mean pressure;
V02 = oxygen consumption (STPD); HR = heart rate; CI = cardiac index; SI = stroke index; SERI = systolic
ejection rate index; LVSWI = left ventricular stroke work index; TTI = modified tension-time index; dp/dt = first derivative of left ventricular systolic pressure curve; pCO2 = partial pressure of carbon dioxide; PO2 = partial pressure of oxygen; sat = oxygen saturation. Values shown are means and standard deviations.
Table 1 shows a summary of the control,
pacing, and post-pacing hemodynamic data
for all patients. Table 2 shows the significance
of change in any measured parameter during
the initial study period. The average heart
rates were similar in each group during the
control period. The pacing rate chosen for the
group which developed angina varied from
125 to 160 and averaged 140. The average rate
for the non-angina group was 140 and for the
normal subjects 142. The cardiac index during
the control period was similar in each group
and did not change significantly during the
period of pacing. Consequently the stroke
index fell by approximately 45% in each group
during the period of pacing. The mean
brachial artery pressure was similar in the
normal and non-angina groups during the
control period. There was a small but
significant rise in mean brachial artery
pressure in the non-angina group during
pacing, but no change in the normals. The
mean brachial artery pressure in the angina
group was 11 mm Hg higher than that in the
normal subjects during the control period and
rose during pacing from 101 to 119 mm Hg.
The left ventricular stroke work index fell
during pacing by 40% in the normal group and
by 31% and 33% in the angina and non-angina
groups (fig. 1).
There was no significant difference in left
ventricular end-diastolic pressure during the
control period among the three groups (fig.
2). The mean value in each group was
between 8 and 9 mm Hg although one patient
in the angina group and one in the non-angina
group exceeded normal (12 mm Hg). In the
non-angina and normal groups, the mean left
ventricular end-diastolic pressure showed an
immediate decline at the onset of pacing from
an average value of about 9 mm Hg to
between 2 and 3 mm Hg where it remained
for the duration of the pacing period (fig. 3).
In the angina group the initial fall in left
ventricular end-diastolic pressure was less
marked reaching 5 mm Hg in the early pacing
period. This subsequently rose progressively
throughout the period of pacing reaching an
average of 9.5 mm Hg at the end of pacing. In
four patients it exceeded normal. The large
standard error in the angina group indicates
Circulation, Volume XXXIX, June 1969
CARDIAC FAILURE DURING ANGINA PECTORIS
TTI
(mm Hg/
min X 10-1)
dp/dt
(mm Hg sec)
1138 ±4 296
2246 4: 500
1118 i 267
1466 392
203
144
153
1041
1176
906
4
1675 i 197
749
Brachial artery
pCO2
pH
Pulmonary artery
Sat
(%)
P02
pCO°
pH
(mm Hg)
(mm Hg)
7.40 0.02
7.44 i 0.05
37 3.0
33 4: 6.5
74 8.3
82 4 10.5
95
96
1.7
1.8
7.39 0.02
7.42 i 0.04
38 4.5
37 ±t 4.7
1183 i 410
1687 i 271
7.40 i 0.04
7.43 0.05
37 4.0
34 4± 2.3
76 i 6.7
82 9.2
95
96
1.2
1.5
7.39 i 0.04
7.40 i 0.05
37
1143 i 252
1471 i 299
7.42
36
95
2.5
7.41
0.05
39
95 i 2.3
7.42
0.05
38 i 3.9
0.04
7.43 i 0.04
4.2
35 i 3.1
78
±4
11.1
76 i 10.2
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considerable variability in left ventricular enddiastolic pressure during the pacing period,
the range during the final minute of pacing
being 3 to 27 mm Hg. These variations
appeared to be unrelated to the site of
pacing.
On interruption of pacing at any time the
left ventricular end-diastolic pressure increased rapidly reaching a stable level in two
or three beats and was measured over the next
two respiratory cycles. The mean value for
the left ventricular end-diastolic pressure
during interruption at intervals throughout the
pacing period is shown in figure 3. In the
normal
(mm Hg)
group
the filling
38
4
4.8
38
pressure
Normal group
C-P*
<0.001
NS
0.02
<0.001
NS
<0.001
V02
HR
CI
SI
SERI
LVSWI
TTI
dp/dt
<0.001
<0.001
<0.001
(0.01 t)
(NSt)
NS
0.01
NS
NS
<0.001
<0.001
NS
NS
NS
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
0.05
<0.001
<0.001
<0.001
<0.001
<0.001
C-P = significance of change between control and pacing periods.
t Values for C-PP = significance of change between control and immediate post-pacing periods.
*
For other abbreviations
Circulation, Volume XXXIX, June 1969
see
footnote of Table 1.
3.4
38 i 3.5
during
interruption returned to control values.
Similar results were seen in the non-angina
group although these values were slightly
greater than the control values. In contrast the
angina group showed a rise to abnormal levels
during interruption even within the first 2 min
of pacing, usually before the onset of pain.
The pressures during interruption continued
to rise throughout the period of pacing
reaching 21.7 mm Hg at the termination of
pacing. The highest post-pacing pressures
were observed in those patients who exhibited
an abnormally elevated left ventricular end-
Non-angina group:
C-P*
(<0.001t)
3.1
4.1
42 i 7.9
37 i 3.4
Angina group:
C-P*
PAm
38
36
3.5
2.3
Table 2
Summary of Significance of Changes (P Values) During Pacing Study
BAm
LVEDP
PO0
(mm Hg)
750
PARKER ET AL.
LV EDP
mm Hg
26
24
+|
22
INTERRUPT
\
20
18
16
14
'it,,
ANGINA
12
60
PACING
i
8
6-
4
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2
14
---
NON -ANGI NA
\
6
INTERRUPT
-
4 -
PACING
2
14
12
~---j
10
INTERRUPT
8
NORMAL
4
PAC(NG
2
O
5-6
3-4
e-9- i0
MINUTES OF PACING
1-?
CONTROL
Figure 3
The average left ventricular end-diastolic pressure
(LVEDP) and standard error are shown for each of
the three groups during the control period, at intervals
throughout the pacing period and at points of interruption. In the normal and non-angina groups, the
LVEDP falls during the early pacing period and
remains low throughout the period of pacing. At
points of interruption the LVEDP returns to near
control values. In the angina group there is a small
initial decrease in LVEDP, but this gradually returns
to control values. The LVEDP during periods of interruption is abnormal throughout the pacing period.
diastolic pressure during pacing. The abnormal rise in left ventricular end-diastolic
pressure during interruption of pacing is
shown in figure 4. Following cessation of
pacing this pressure remained elevated for
periods varying from 20 sec to 6 min. When
the pressure elevation persisted for more than
1 min, it was usually accompanied by
continued pain and S-T segment depression
(fig. 5). The dp/dt rose 29% to 42% during
pacing, but there was no significant difference
among the three groups. The tension-time
index rose in all groups, but this was greatest
in the angina group and is related to the
abnormal rise in systemic pressure during
pacing. In the angina and non-angina groups
during pacing there was an increase in arterial
blood pH, PO2, and oxygen saturation and a
decrease in pCO2. This pattern of respiratory
alkalosis, probably due to hyperventilation,
was not seen in the normal group.
The 20 patients studied after administration
of nitroglycerin consisted of six patients in the
angina group, seven in the non-angina group,
and seven normal subjects. During pacing
after nitroglycerin, only one of the angina
group developed pain. Table 3 shows the data
from both study periods in these patients and
table 4 shows the significance of change in
any measured parameter during these studies.
The pertinent observations are summarized in
figures 6 to 8. The average values for heart
rate, cardiac index, left ventricular enddiastolic pressure, and left ventricular stroke
work index correspond closely in the three
groups during the initial control period
(control I) and before administration of
nitroglycerin (control II). Following nitroglycerin (control NG) heart rate rose and
cardiac index, systemic pressure, left ventricular end-diastolic pressure, and left ventricular
stroke work index declined in each group, but
these changes were not always of statistical
significance. Following nitroglycerin there was
a fall in left ventricular end-diastolic pressure
of approximately 50% in all groups.
During pacing there was a further decline
in left ventricular end-diastolic pressure in all
groups to approximately 2 mm Hg. This is in
Circulation, Volume XXXIX, June 1969
(CARLIJAC FAILURE DURING ANGINA PECTORIS
A\N'(-.P:.2
160
160
I3A
4
A
1
V
U
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I
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..
751
1--
PACINC,
ST(VITITA)
Figure 4
1 't ventricular end-diastolic pressure (LVEDP) in a patient experiencing angitna during
pacing. The LVEDP is normal during pacing but rises quickly during interruption to abnornal
levels and falls with reinstitution of pacing.
LVEDp 20
mmlHg
I
0EC
ECGJ
30-
PACING - FAST TRACING
PACING
CONTROL
N
LVEDP 20-P
mmHg 10-
,s
/
t~
~
~
~
~ ~~
~
~
~
~
~
~~~~~~~~~~~~~~~~~~~~..
W.
.*M
0ECG
0-w-
IMMEDIATE
POST PACING
FOUR MIN.
POST PACING
ONE Ml N.
POST PACING
SIX MIN.
POST PACING
F'igure 5
ventricnlao cndI-diastolic preZssice (LVEDP) during pacing anid at initere;als dutIin, the
still experiencintg anigina. The LVEDP is still abnormal
post-pacitig period twhen the patient
6 mzn after cessation of pacinig.
Left
was
inlitial pacing period where
there was no fall in left xventricular enddiastolic pressure in the angina group. Oin
cessation of pacinig tlhe miiean values in eaclh
group rose to approximate the control values.
Only one patient of any group exceeded
conitraist to the
(&
IL;.,
-I
Volumne
XXXIX,
Juni
1969
norinal values during the post-pacing period,
and this was the single patient xvho developed
angina despite the prophylactic administration
of initroglycerin, where the post-paciing left
ventricular end-diastolic pressure reached 30
Hg. The left ventricular stroke work index
mm
752
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CARDIAC FAILURE DURING ANGINA PECTORIS
753
Table 4
Summary of Significance of Change (P Values) During Pacing Study Before and After
Nitroglycerin
C 1-P1
C2-CNG
CNG P2
P
i-P2
Angina grouip
BAm
LVEDP
P = 0.02
NS
NS
P < 0.001
PAm
(P < 0.001*)
P = 0.02
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\V02
NS
HR
CI
SI
SERI
LVSWI
TTI
dp/dt
P < 0.001
NS
P < 0.001
P <0.001
P < 0.001
P = 0.005
NS
NS
NS
(P = 0.05t)
P = 0.025
NS
NS
NS
P = 0.05
P = 0.01
P = 0.005
P = 0.05
P = 0.05
NS
NS
NS
P = 0.005
P = 0.05
P <0.001
P < 0.001
P = 0.02
P < 0.001
P = 0.01
P <0.001.
(P < 0.001I
P <0.001
NS
NS
P = 0.05
P = 0.05
NS
P = 0.05
P = 0.01
NS
Non-angina group
BAm
LVEDP
P = 0.005
P <0.001
(P = 0.025*)
PAm
HR
CI
SI
=
0.01
P = 0.02
(P = 0.05t)
NS
(P = 0.005t)
P = 0.005
NS
NS
NS
P < 0.001
P = 0.01
P < 0.001
NS
NS
NS
NS
NS
P = 0.01
P = 0.02
P = 0.02
P < 0.001
P = 0.005
NS
NS
P
P
P
P
SERI
LVSWI
TTI
dp/dt
P = 0.02
NS
P <0.001
P
NS
NS
V02
NS
< 0.001
<0.001
= 0.005
< 0.001
NS
P < 0.001
P < 0.001
NS
NS
NS
NS
P < 0.001
NS
NS
Normal group
BAm
LVEDP
NS
P <0.001
P = 0.005
P = 0.01
(Ns*)
PAm
NS
NS
V02
HR
CI
SI
SERI
LVSWI
TTI
P
P
P
P
<0.001
= 0.05
< 0.001
= 0.01
P = 0.005
P <0.001
P = 0.02
dp/dt
Values in parentheses
are:
* for C I-PP1;
similar in all groups during control I and
but fell following administration of nitroglycerin. During pacing after nitroglycerin
there was a further fall in left ventricular stroke
work index. The left ventricular stroke work
index was lower than during the initial pacing
was
II
Circulation, Volume XXXIX,
June
1969
P
=
0.005
NS
(NS t)
P < 0.001
(P
P = 0.002
NS
NS
P = 0.005
P = 0.005
NS
P
=
P
P
P
P
<
<
<
<
P
=
P
=
0.02
NS
P = 0.02
NS
NS
t for CNG-PP2;
NS
NS
0.005
0.001
0.001
0.001
0.001
0.05
=
0.025t)
NS
NS
NS
NS
NS
NS
NS
NS
NS
I for PP1-PP2.
period in the angina and non-angina groups
but not significantly different in the normal
subjects.
Discussion
It is not immediately apparent
why
left
PARKER ET AL.
75l-4
-ANGINA
- - - NON-ANGINA
NORMAL
HEART RATE
150F
LVEDP
mm Hg
--- ANGINA
- NON-ANGINA
O
NORMAL
25r
NITROGLYCERIN
NITROGLYCERIN
20F
1'
1O00
15p
'/
/
o
\
/
I
Vi
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50
5
(
l1 l
CONTROL-I
PACING
I
CONTROL-NG
PACING
CONTROL-I!
Figure 6
The heart rates in each of the three groups during the
study periods before and after administration of
nitroglycerin. The control heart rates were similar in
each of the three groups during both study periods.
The heart rates increased after the administration of
nitroglycerin, but the heart rates were similar during
each period of pacing.
ventricular end-diastolic pressure should not
rise during angina induced by pacing as
earlier work in man has repeatedly shown
myocardial ischemia to be associated with
elevated left ventricular filling pressure'-3 5-t1
and impaired left ventricular contractility.3-' 9, 19 Similar observations have also been
reported in animals with experimental
myocardial ischemia.20' 21 The problem, however, may be resolved when left ventricular
end-diastolic pressure and left ventricular
stroke work are examined together (fig. 9). In
the normal subjects the cardiac output was
unchanged during pacing and there was
subsequently a decline in stroke volume and
stroke work of approximately 40%. In
accordance with the Starling relationship,
PACING
CONTROL-7TI
|
PACING
PACING
CONTROL-NG.
PACING
CONTROL-I
STOPPED
STOPPED
Figure 7
Left ventricular end-diastolic
pressures (LVEDP) for
the two study periods in those patients who received
nitroglycerin. The LVEDP falls after nitroglycerin
and decreases further in each group during the pacing
period. The abnormalities in LVEDP during pacing
and in the post-pacing period seen in the angina
group during the initial study are not present following the administration of nitroglycerin; then all three
groups behave in a similar fashion.
there was a decrease in left ventricular enddiastolic pressure. The values obtained durinig
the control and pacing period describe a
different type of ventricular function curve in
which left ventricular stroke work is varied by
rate change alone, as contrasted to the usual
methods involving blood volume changes,22-25
exercise,26 or drug administration.27 This type
of ventricular function curve in addition to the
Starling mechanism includes the Bowditch
phenomenon wherein an increase in myocardial contractility results from an increase in
heart rate,28 but this factor is common to all
groups studied in this manner. When left
ventricular stroke work is increased by the
Circulation, Volume XXXIX, June 1969
CARDIAC FAILURE DURING ANGINA PECTORIS
755
LVSWI
GM-M/M2
80 r
55-
------ANGINA
- - - NON-ANGINA
NORMAL
50-
NITROGLYCERIN
45 F
I
40 L
70h
60 F
50o
LV
STROKE
WORK
INDEX
GM-M/M2
ON,
40F
C
P PP
ANGINA A Aii
NON-ANGINA O __!JP
NORMAL O *1
30r
"X
,
\"\~
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30F
25 F
20-
20
O0
5
-.
(
CONTROL-I
PACING
CONTROL-NG
PACING
CONTROL-II
0
5
10
LVEDP
mm Hg
15
20
25
Figure 8
Figure 9
Left ventricular stroke work index (LVSWI) for patients studied before and after nitroglycerin. The
LVSWI declines after administration of nitroglycerin
and decreases further during pacing in the angina
and non-angina groups.
Relationship between the left ventricular end-diastolic
pressure (LVEDP) and the left ventricular stroke work
index (LVSWI) in the three groups of patients during
the control (C), pacing (P), and post-pacing (PP)
periods. In the normal and non-angina groups the
decrease in LVSWI accompanying the increase in
heart rate is associated with a reduction in LVEDP
according with the Starling relationship. The patients
in the angina group, however, show no change in
LVEDP with the decrease in LVSWI and thus change
from a normal to an abnormal ventricular function
curve when ischemia develops. Depression of ventricular function persists for a variable time during
the post-pacing period.
cessation of pacing, the left ventricular enddiastolic pressure returns along the previously
established curve. In the non-angina group,
the control, pacing, and post-pacing points
follow along this line previously described by
the normal subjects. On the other hand, the
angina patients in spite of a similar decrease
in left ventricular stroke work during pacing
do not exhibit a decrease in left ventricular
end-diastolic pressure. This pressure, even
though within an apparently normal range, is
actually elevated for the reduced left
ventricular stroke work. This abnormal
relationship is illustrated by the dotted line
showing the movement to a depressed
ventricular function curve. This concept is
supported by the marked elevation of left
ventricular end-diastolic pressure that occurs
as left ventricular stroke work is suddenly
Circulation, Volume XXXIX, June 1969
increased by the abrupt fall in heart rate at
the cessation of pacing and this second point
outlines the upper portion of- the depressed
ventricular function curve. The gradual return
of left ventricular end-diastolic pressure to
normal indicates that depressed left ventricular function is a reversible phenomenon
accompanying myocardial ischemia. All points
during control and pacing periods were obtained from hemodynamic data. The post-pacing points were however constructed assuming
7S6
PARKER ET AL.
50E-
45[A
40L
C
CN
P2
PP2
Al
ANGINA A
_A_
NON -ANGINA 13 OOy
NORMAL _ O __I
25
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I
20F
_.1.
0
5
10
.
__
..
__
15
..-.
I.
__
._ 1--
LVEDP
mm Hg
20
__
25
Figure 10
Relationship between the left ventricular end-diastolic
pressure (LVEDP) and the left ventricular stroke -ork
index (LVSWI) in the three groups of patients during
sintus rhythm before (C II) and after (C NG) nitroglycerin, during pacing (P2) and in the post-pacing
period (PPJ). All groups now are on the normal
ventricular function curve. The one patient who experienced angina during this second pacing period
again showed depressed ventricular performance and
is not included in this figure.
that the cardiac output in the immediate post-
pacing period was equal to that during the
control and pacing periods. This assumption
constant cardiac output seems justified in
our present findings and other reports
indicating that cardiac output is not signifi-
of
a
view of
cantly affected by changes in rate over the
used.'2'29' 30 This may, however, not be
the case in the early post-pacing period in the
angina group. The imposition of a sudden
volume load on the ischemic ventricle inight
well result in a fall in cardiac output in the
early post-pacing period. This would imply an
even more depressed ventricular function
curve than is represented.
ranges
Results during the nitroglycerin studies
support the concept that left ventricular
function is depressed during myocardial
ischemia and that the elevation of the postpacing left ventricular end-diastolic pressure is
subsequent to decreased ventricular contractility resulting from myocardial ischemia. Five
of the six patients of the angina group did not
experience pain during pacing after nitroglycerin and displayed a relationship between left
ventricular end-diastolic pressure and stroke
work during control, pacing, and post-pacing
periods similar to the normal and the nonangina groups (fig. 10). The one patient who
experienced angina during pacing despite the
administration of nitroglycerin continued to
show depression of ventricular funiction
during the pacing and post-pacing periods.
This return from a depressed ventricular
function curve to a normal one by the
administration of nitroglycerin indicates that
abnormal left ventricular filling pressures
during angina are not due to chronic
alterations in ventricular compliance as
previously suggested.7 These observations do
not rule out temporary, reversible change in
ventricular compliance during myocardial
ischemia, but changes in ventricular perforiuance seem more likely.
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Reversible Cardiac Failure During Angina Pectoris: Hemodynamic Effects of
Atrial Pacing in Coronary Artery Disease
JOHN O. PARKER, J. RODNEY LEDWICH, ROXROY O. WEST and ROBERT B.
CASE
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Circulation. 1969;39:745-757
doi: 10.1161/01.CIR.39.6.745
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