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Myocardial function during atrial pacing in patients with angina pectoris and normal coronary arteriograms
SEPTEM BER 7, 1973
The American
Journal-of CARDIOLOGY VOLUME 32 NUMBER 3
CLINICAL STUDIES
Myocardial Function During Atrial Pacing in Patients with Angina Pectoris and Normal Coronary Arteriograms Comparison with Patients Having Significant Coronary Artery Disease
ROBERT ARBOGAST, MD, MSc* MARTIAL G. BOURASSA, MD, FACC
Montreal, Quebec
From the Montreal Heart Institute and the Department of Medicine, University of Montreal School of Medicine, Montreal, Quebec, Canada. This work was supported by research funds from the J. L. Levesque Foundation and the National Health and Welfare of Canada, Project 604-7-672. Manuscript accepted February 7, 1973. *Present address: University of California at Davis, Medical School, Section of Cardiology, Davis, Calif. 95616. Address for reprints: Martial G. Bourassa, MD, Montreal Heart Institute, 5000 East, Belanger St., Montreal 410, Quebec, Canada.
Right atrial pacing at 140 beats//min for 8 minutes induced an electrocardiographic "ischemic pattern" in 10 patients with normal coronary arteriograms and chest pain usually typical of angina pectoris (group X). The findings were compared with those in 11 patients with demonstrable coronary arterial stenosis who had the same electrocardiographic "ischemic pattern" during pacing (group C). Six patients of group X and eight patients of group C experienced angina during pacing. In addition, a low level of myocardial extraction (less than 10 percent) or production of lactate was observed during pacing in five patients of group X and in seven of group C. Patients of group X showed a significant rise in cardiac index (P <0.05) and left ventricular minute work index (P <0.01), a significant reduction in left ventricular end-diastolic pressure (P <0.01) and unchanged systemic vascular resistance. In contrast, patients of group C showed a significant lowering of cardiac index (P <0.01), unchanged left ventricular minute work index and left ventricular end-diastolic pressure and increased systemic vascular resistance (P <0.001). "Pacing ventricular function curves," obtained by plotting left ventricular stroke work index against left ventricular enddiastolic pressure, showed marked differences between the two groups. Although the clinical, electrocardiographic and metabolic manifestations were similar in both groups, the mechanism underlYing these abnormalities is probably different. Indeed, if patients with the anginal syndrome and normal coronary arteries had myocardial ischemia, they should, like patients with coronary artery disease, exhibit a depressed or unchanged rather than enhanced left ventricular function during pacing stress.
Several recent studies have stressed the paradox of patients who h a v e both angina pectoris and normal coronary arteriograms. T M These patients cannot be distinguished clinically from patients with coronary artery diseaseZ,2,5; they often show an "ischemic" electrocardiographic pattern 1,2 and, in some cases, biochemical evidence of myocardial ischemia during stress. 1,3,6,7 A previous study 5 found no
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MYOCARDIAL FUNCTION DURING ATRIAL PACING--ARBOGAST AND BOURASSA
mg, and local anesthesia. A no. 7F Cournand catheter was placed in the mid portion of the coronary sinus through an antecubital vein, and its position was verified by a small injection of contrast material. A no. 8F, type R P X 063 polyethylene catheter (Becton and Dickinson Co.) was positioned in the left ventricle by a retrograde percutaneous femoral arterial technique. A no. 6F bipolar electrode catheter (USCI) was positioned at the entry of the right atrium through a percutaneous femoral vein approach. Ten minutes after introduction of all catheters, left ventricular and aortic pressures were recorded at normal and high levels of sensitivity at recording speeds of 25 and 100 mm/sec, I0 ml of blood was sampled from the coronary sinus and ascending aorta and a dye-dilution curve was obtained by injection in the coronary sinus and sampling in the aorta at a speed of 20 ml/min with use of a calibrated Harvard pump. Then, atrial tachycardia was induced by connection of the electrode catheter to an external pacemaker (Medtronic demand model 5840). The heart rate was rapidly increased to approximately 140 beats/min, and a 12 lead electrocardiogram recorded; whenever second degree atrioventricular block developed or the duration between the R wave and the following spike induced by the pacemaker was less than 0.10 second, pacing was stopped and 0.8 m g of atropine sulfate was administered intravenously. After 2 minutes, pacing was restarted. The stimulation was adequate in all patients under these conditions. After 8 minutes of stimulation, or 5 minutes after the appearance of chest pain, the recordings and samplings were repeated. Diagnostic left ventricular cineangiograms and selective coronary arteriograms in multiple projections were then obtained as previously described. 9 Interpretation of the coronary anglograms was routinely performed by three radiologists. Significant coronary artery disease was diagnosed as any stenosis equal to or greater than 50 percent of one or more major coronary arteries.
significant differences in the h e m o d y n a m i c d a t a at rest a n d during exercise of these p a t i e n t s a n d those with d e m o n s t r a b l e coronary artery disease. This c o m m u n i c a t i o n is the first to r e p o r t the influence of a s t a n d a r d i z e d atrial pacing stress test on h e m o d y n a m i c indexes in p a t i e n t s w i t h o u t coronary artery disease b u t a definite " i s c h e m i c " electrocardiographic p a t t e r n during the test. T h e d a t a are c o m p a r e d with d a t a o b t a i n e d u n d e r the s a m e conditions in patients with coronary artery disease who h a d the s a m e clinical a n d electrocardiographic findings during pacing. Methods Patients
Ten patients with a definite electrocardiographic "ischemic" pattern during atrial pacing, angina pectoris (typical in six and atypical in {our) and normal or near normal coronary arteriograms (group X) were studied. The data were compared with those of 11 patients who had the same electrocardiographic abnormalities during pacing and who had angina pectoris (typical in eight and atypical in three) and demonstrable stenosis of one or more coronary arteries {group C). Chest pain in all patients was defined according to the criteria of Hurst and Logue. s Patients with abnormal heart sounds or murmurs, diastolic blood pressure greater than 100 mm Hg, clinical evidence of cardiac failure or abnormal heart size on X-ray examination, abnormal S - T segment on the resting electrocardiogram or recent intake of digitalis and beta blocking agents were excluded. Investigative Procedure
All patients were studied in the fasting state after premedication with meperidine, 50 mg, and phenergan, 25 @ TABLE I
Values Obtained at Rest and During Atrial Pacing in Patients of Both Groups (means ± standard error of the mean)
Sex
Age (yr)
Condition
HR
AoP
TTI
LVEDP
Cl
TPR
LVMWI
LVSWI
LVSPI
4834 ±564 6104 ±508 +1269 ±384
61.6 ±5.01 43.0 ±3.46 --18.6 ±3.09
214 ±19 210 ±16 --3.6 ±11.0
4699 ±478 4508 ±294 --191 ±279
60.1 ±4.81 31.1 ±2.08 --29.0 ±3.44
201 ±16 158 ±13 --42.7
Group X (Angina Pectoriswith Normal CoronaryArteriogram) (no. = 10) M 4; F6
37 ±1.9
Rest Pacing A
78 ±5.0 141 ±1.5 .1.67 ±2.9
95.9 ±4.63 106.4 ±4.42 +10.5 ±3.31
2390 ±164 3289 ±155 ,1,899 ±168
9 ±0.86 3.5 ±0.58 --5.5 ±0.50
3.62 ±0.35 4.06 ±0.30 +0.44 ±0.19
1395 ±122 1356 ±110 --39.5 ±34.4
Group C (Angina Pectoriswith CoronaryStenosis)(no. = 11) M 11; F0
48 ±2.1
Rest Pacing
78 ±3.5 145 ±2.2 .1.63 ±4.9
93.8 ±5.19 107.7 ±4.30 .1.13.9 ±4.0
2475 ±221 3356 ±198 .1.880 =1=196
10.55 ±0.78 12.82 ±1.87 ,1,2.27 ±1.86
3.59 ±0.27 3.28 ±0.29 --0.32 ±0.09
1182 ±90 1561 ±157 .1.379 ±93
±11.3
AoP = mean aortic pressure (mm Hg); CI = cardiac index (liters/min per m=); HR = heart rate (beats/min); LVEDP = left ventricular end-diastolic pressure (mm Hg); LVMWl ---- left ventricular minute work index (g-m/min per m2); LVSPI = left ventricular stroke power index (g-m/sec per m2); LVSWl ----left ventricular stroke work index (g-m/systole per m2); TPR = total peripheral resistance (dynes sec cm-s); TTI ----tension-time index (mm Hg sec/min). A ----mean difference between values obtained at rest and during pacing.
258
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The American Journal of CARDIOLOGY
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MYOCARDIAL FUNCTION DURING ATRIAL PACING--ARBOGAST AND BOURASSA
The pressures were recorded through a fluid-filled left ventricular catheter directly connected to a S t a t h a m P23Db strain gauge on a photographic r e c o r d e r (Honeywell Visocorder oscillograph model 1612). All pressure determinations were averaged over 10 consecutive beats. Left ventricular end-diastolic pressure was measured at the coincidence point of the downslope of the ventricular a wave and the initial left ventricular pressure upstroke. During pacing-induced tachycardia, this point could not be determined in some cases; in the latter,-we measured the lowest point before the initial left ventricular pressure upstroke which occurs very near the peak Of the R wave of the electrocardiogram (lead II), as reported by others. 1° M e a n aortic pressure was d e t e r m i n e d electronically. M e a n aortic systolic pressure was calculated by p l a n i m e t r y of the area between the onset of the pressure upstroke a n d the trough of the dicrotic notch according to the formula: M e a n aortic systolic pressure = s -1 f o P(t) dt, where s is the ejection time and P the pressure at instant t. Cardiac output was d e t e r m i n e d by the dye-dilution technique, and the area under the dye curve was calculated according to the method of W i l l i a m s et al. 11 Injection of dye was performed with a precision syringe (BD Cornwall Luer-lok) in order to inject exactly the same a m o u n t of dye during each period. A standard 12 lead electrocardiogram was recorded at rest and every 30 seconds during atrial pacing on a conventional electrocardiograph (Hewlett-Packard a u t o m a t i c cardiograph model 1513 A). T h e criteria for a positive "ischemic" p a t t e r n were a straight S - T segment depression of 1 m m (0.1 mv) or more, with a m i n i m a l duration of 0.08 second and a horizontal or descending slope in any lead during atrial pacing. Lactate determinations were performed in duplicate according to the e n z y m a t i c method of Hohorst. 12 A variation coefficient ( s t a n d a r d d e v i a t i o n / m e a n × 100) of 5.14 percent was found with this technique in our laboratory using 26 s t a n d a r d samples. M y o c a r d i a l extraction was cal-
TABLE II Summary of the HemodynamicResults Difference Between Restand Pacing
Heart rate Mean aortic pressure Tension-time i n d e x Left ventricular end-diastolic pressure Cardiac i n d e x Total peripheral resistance Left ventricular minute work index Left: ventricular stroke work index Left ventricular stroke power i n d e x
Difference
GroupX
Group C
Between Groups
t *** t * ~' * * * ,~ * * *
~ *** t ** t*** NS
NS NS NS ***
t * NS
~ ** t ***
*** ***
t **
NS
**
~ ***
~ ***
*
NS
~ **
*
NS = not significant; * = P <0.05; * * = P <0.01; * * * = P <0.001; t = significant increase during pacing; $ = significant decrease during pacing.
AoP I (mm Hg) 140
GROUP X
GROUP C
t =3.17
t =3.48
P < 0.025
p < 0.01
orest ~
130
i meanPaCing
120
+S.EM
IO0
9O 80 7O Z~AoP +20 J-
t< 1
.16 I-
N.S.
~TE
+12~
FIGURE 1. Values of mean aortic pressure (AoP) obtained at rest and during pacing in the two groups of patients. ~AoP = mean difference between values at rest and during pacing; N.S. = not significant; p = probability; S.E.M. = standard error of the mean.
culated by the equation: Extraction (%) = (value in aorta - value in coronary sinus)/value in aorta × 100. The following formulas were used in the calculations:. Total peripheral resistance (dynes sec cm -5) = mean aortic pressure x 1,332/cardiac output (liters/rain) × 103/60. ( . Tension-time index (ram Hg sec per mln) = mean aortic systolic pressure × ejection time (seconds) x heart rate (beats/rain). Left ventricular minute work index ( g - m / m i n per m 2) = (mean aortic systolic pressure - left ventricular enddiastolic pressure) x cardiac index (liters/rain per m 2) x 13.6. Left ventricular stroke work index (g-m/systole per m 2) = left ventricular minute work i n d e x / h e a r t rate. Left ventricular stroke power index (g-m/sec per m 2) = left ventricular minute work index/injection time. All calculations were performed with a Hewlett-Packard model 9100-A calculator using the same program. S t a t i s t i c a l a n a l y s i s : The difference between hemodynamic indexes obtained at rest and during pacing was tested against zero using a t test for paired data. For each index, the difference between the two periods was calculated and expressed as 4. The A value obtained was compared between groups by a t test for grouped data.
Results D u r i n g p a c i n g , a n g i n a p e c t o r i s o c c u r r e d in six p a t i e n t s of g r o u p X ( a n g i n a p e c t o r i s w i t h n o r m a l a r t e r i o g r a m ) a n d e i g h t p a t i e n t s of g r o u p C ( a n g i n a p e c toris with coronary stenosis). All hemodynamic findings a r e s u m m a r i z e d i n T a b l e s I a n d II. Heart rate: Heart rates at rest and during pacing a n d t h e i n c r e m e n t i n d u c e d b y p a c i n g were n o t significantly different between groups.
September7, 1973 The AmericanJournalof CARDIOLOGY Volume32
259
MYOCARDIAL FUNCTION DURING ATRIAL PACING--ARBOGAST AND BOURASSA
TTI
GROUP X
GROUP C
(mmHg. sec/min)
t=5.34
t =4.48
p< 0.001
p
• 4400
LVEDP
GROUP X
(ram Hg)
t=-11.00
t=1.22
p < 0.001
N.S.
25
o rest
4000'
GROUP C
o rest
• pacing mean
3600
• pacing
20-
"~-+S.E.M
3200
15
2800
10
Q,
2400 5 2000 LVEDP
1600 ATT/1200 :
t =3.86
+6.+4
l
t
p < 0.001
+2 0 -2 + 400 F
--4=
i
0FIGURE 2. Values of tension-time index (TTI) obtained at rest and during pacing in the two groups of patients. ATTI = mean difference between values at rest and during pacing.
Mean aortic pressure: This value increased significantly in both groups during pacing; however, the increment was not different between goups (Fig. 1). Tension-time index: Pacing induced a highly significant and similar increase of tension-time index in both groups (Fig. 2). Left ventricular end-diastolic pressure: During atrial pacing, left ventricular end-diastolic pressure
CI (i/min/m2) 7
GROUP X
GROUP C
t =2.27 p<0.05
t=-3.63 p< 0.005
6 FIGURE 3. Values of left ventricular end-diastolic pressure (LVEDP) obtained at rest and during pacing in the two groups of patients. ~ L V E D P = mean difference between values at rest and during pacing.
decreased significantly in group X (P <0.001) but was not significantly changed in group C. The variation of left ventricular end-diastolic pressure (A) induced by pacing was significantly different between groups (P <0.001) (Fig. 3). Cardiac index: This index was significantly altered in both groups, increasing in group X (P <0.05) and decreasing in group C (P <0.01). The
GROUP X o rest
(dynesT.Ps~c.cm.5) 220^~
°F
• pacing
GROUP C
t=-l.15
l= 4.06
I
N.S.
p< 0.001
I
ooo -
,oo1-
//
//
I °re,'
I
1600
2 1 ~Cl
. 0 . 6 I+0.41-
t=3.69
p < 0.001 ATPR [+300~
-0.2~ -0.4 -0.6
•,oo
p <0.001
N
-lOOp
FIGURE 4. Values obtained at rest and during pacing for cardiac index (CI) in liters per minute per square meter body surface area. ACh = mean difference between values at rest and during pacing.
FIGURE 5. Values obtained at rest and during pacing for total peripheral resistances (TPR). ATPR = mean difference between values at rest and during pacing.
260
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The A m e r i c a n Journal of C A R D I O L O G Y
MYOCARDIAL FUNCTION DURING ATRIAL PACING--ARBOGAST AND BOURASSA '
® 2000 group ~ ~
1500-
".,,
• LVSWI '(g.m/sys.t./m2) 70
A LVMWI (g-m/min/m 2)
} mean -+S.EM
o group X
• group C
60
100050
"-.500
,/"
\
\
-
40 l÷"
""-I I ,2t ,3 4, ,~ ,6 ~tvEDP (ram Hg) •
"
I"
oroop
p< 0.01
~z
30
C
FIGURE 6. Plotting of changes of left ventricular minute work index (ALVMWI) against changes of left ventricular end-diastolic pressure (ALVEDP) induced by atrial pacing in the two groups of patients.
variation of cardiac index was significantly different between groups (P <0.001) (Fig. 4). Total peripheral resistance: A significant variation was found only in group C (P <0.001). This variation was significantly different between groups (P <0.001) (Fig. 5). Left v e n t r i c u l a r w o r k indexes: Left ventricular minute work index was unaffected by pacing in group C and was increased in group X (P <0.01). When the change in left ventricular minute work index (A) is plotted against the change in left ventricular end-diastolic pressure, the variation of left ventricular minute work index is clearly different between groups (Fig. 6). Left ventricular stroke work index, although significantly lowered in both groups during pacing (P <0.001), was less modified in group X (P <0.05) and was significantly higher in this group during pacing (P <0.01). "Pacing ventricular function curves" were obtained by plotting left ventricular stroke work index against left ventricular end-diastolic pressure. For each patient, the line between rest and pacing values forms an angle (~) with the abscissa. This angle was calculated by the following equation: Tangent a = A left ventricular stroke work index/A left ventricular end-diastolic pressure or a = arch tangent of (A left ventricular stroke work index/A left ventricular end-diastolic pressure), where arch tangent is the inverse function of tangent. The mean values expressed in degrees (4- standard error of the mean) were 65.2 (±3.9) and 93.6 (4-4.1) in groups X and C, respectively. The difference between the groups was highly significant (P <0.001) (Fig. 7). Left ventricular stroke power index was not affected by pacing in group X but decreased significantly in group C (P <0.01) (Fig. 8). Myocardial lactate extraction: In both groups, myocardial lactate extraction was reversed to production during pacing in some patients (three of group X and four of group C). A low level of extraction (less than 10 percent) or production was observed during pacing in five patients of group X and in seven of group C (Fig. 9).
I I
I
2
4
I
I
I
I
I
I
6 8 10 12 14 16 LVEDP (mm Hg) F I G U R E 7. "Pacing ventricular function curves" obtained by plotting mean values of left ventricular stroke work index (LVSWI) against mean values of left ventricular end-diastolic pressure (LVEDP). The slopes of the curves or the angles which form these slopes with the abscissa for the two groups of patients are significantly different (P <0.001) (see text for explanation). Mean values of left ventricular stroke work index obtained during pacing are significantly different between the two groups (P <0.01).
Effect of administration of atropine: For all variables, there was no significant difference among patients who did and did not receive atropine when all patients or patients in the two groups were considered separately. Discussion
~'
In patients with normal coronary arteries, three
possible mechanisms have been suggested for the occurrence of angina pectoris: 13 (1) an abnormal affinity of hemoglobin for oxygenZ~; (2) occlusive disease
LVSPI (g.m/sec/m2)
350i
GROUP X t=-0.33
N.S.
GROUP C t =-3.79 p < 0.005 o rest
• pacing
F
10%17 A LVSPI
"b
t = 2.47 p < 0.025
-20 I -40
-60 FIGURE 8. Values obtained at rest and during pacing for left ventricular stroke power index (LVSPI). ALVSPI = mean difference between values at rest and during pacing.
S e p t e m b e r 7, 1 9 7 3
The A m e r i c a n Journal of C A R D I O L O G Y
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MYOCARDIAL FUNCTION DURING ATRIAL PACING--ARBOGAST AND BOURASSA
LACTATE
60
--
GROUPX
GROUP C
'40 %extraction 20
1o 0 2O
% produclion 40
:;=,ng
60-FIGURE 9. Values obtained at rest and during atrial pacing for myocardial lactate extraction or production.
of small coronary vessels; and (3) failure of the technique of coronary angiography to detect significant stenosis in the major coronary arteries. All these hypotheses postulate a common underlying mechanism: myocardial ischemia as observed in coronary artery disease. There are some discrepancies in natural history between patients with angina pectoris secondary to coronary atherosclerosis and patients with the anginal syndrome and normal coronary arteries. The prognosis tends to be benign in patients without visualized coronary arterial stenosis, and gradual clinical improvement will occur in more than half of these patients during long-term follow-up studies. 1,4 Sudden death and myocardial infarction are probably rare. In the reported cases, small and large coronary arteries were free of disease, and histologic evidence of myocardial necrosis was often absent or localized in the subendocardial layers. ~,1. To our knowledge, myocardial damage leading to chronic cardiac failure has never been reported in such patients. It is therefore conceivable that a metabolic abnormality, perhaps transient, rather than an irreversible anatomic lesion could account for the manifestations observed in these patients. In this study, we attempted to determine--using the same objective index of myocardial "ischemia": namely, electrocardiographic "ischemic" modificat i o n s - w h e t h e r patients with chest pain suggestive of angina pectoris with or without visualized coronary artery disease have the same myocardial functional response during atrial pacing. If true hypoxia occurred in both categories of patients, a similar decrease in myocardial performance should be expected. 1~ Electrocardiographic modifications were used as the criteria for inclusion in the study rather than occurrence of angina in order to avoid the suggestive bias associated with the assessment of angina. In fact, it has been observed in patients with coronary artery disease that pain, "ischemic" electrocardiographic modifications and abnormal myocardial performance ~°,~6,~7 are not necessarily present together. The usefulness of atrial pacing in the assessment of myocardial function in patients with coronary ar262
September 7, 1973
The American Journal of CARDIOLOGY
tery disease has been documented recently. 1°,1s,19 We used a standardized stress test (heart rate abruptly increased to 140 beats/min) in order to study all patients under similar conditions. We have therefore obtained comparable levels of heart rate and tension-time index, predicting comparable levels of myocardial oxygen requirements. The induced heart rate was generally higher than in previous studies, and pacing was always maintained for at least 5 minutes; this technique was preferred to use of short periods of pacing up to the anginal threshold because it has been postulated that relatively long ischemic periods may be necessary to induce ventricular dysfunction. 2° Mechanism of S-T changes and angina pectoris in absence of coronary disease: Most of the hemodynamic changes induced by pacing were significantly different in the two groups of patients (Table II). Mean arterial pressure increased in both groups, a finding noted by others, l°,21 The large decrease in left ventricular end-diastolic pressure during pacing in the group with normal coronary arteriograms (group X) was similar to that seen in normal subjects, whereas considerable individual variations were observed in the patients with coronary artery disease. 1°,17,18,2°,22 Cardiac index, as described by others, 1~ can be lowered in patients with coronary artery disease; however, the decline is not usual, and was probably secondary in our patients to the different technique of pacing stress. In contrast, at a similar heart rate and with the same electrocardiographic modifications, patients of group X had an elevated cardiac index. This finding has never been reported in normal subjects. '28 Despite the higher cardiac index, total peripheral resistance was unchanged, in contrast to findings in the group with coronary artery disease. In addition, pacing ventricular function curves showed marked differences between the two groups. Therefore, we can postulate that the mechanism inducing electrocardiographic modifications in all and angina pectoris in six of the patients of group X is probably not myocardial ischemia. This assertion seems to conflict with the observed electrocardiographic and metabolic modifications. However, both manifestations have been observed in subjects with neurocirculatory asthenia or anxiety neurosis which recently have been suggested to be related to the syndromes observed in our patients. 4 Electrocardiographic modifications of the "ischemic" type have commonly been observed in neurocirculatory asthenia. 24,25 In addition, S - T segment depression is more closely related to metabolic abnormalities than hypoxia itself. 26 Similarly, a relatively greater production of lactate in the peripheral circulation during exercise has been observed in patients with these syndromes. 27 The causative role of increased levels of circulating catecholamines has been suggested. 2s Myocardial lactate production has not been documented in such patients, but experimental data in dogs have shown that during an increase in cardiac metabolic rate induced by isoproterenol, lactate is being excreted rather than utilized. 29 The presence of "ischemic" electrocardiographic modifiVolume 32
MYOCARDIAL FUNCTION DURING ATRIAL PACINGmARBOGAST AND BOURASSA
cations and myocardial lactate production is therefore not necessarily in conflict with the enhanced myocardial performance incompatible with true myocardial ischemia. The discrepancy between our results during pacing and the hemodynamic data previously reported 5 during exercise is unexplained. Pacing is probably a more specific stress for the heart than exercise, which also involves the peripheral circulation, is In addition, the group of patients previously described5 may not have been comparable to our patients; only
3 of these 10 patients experienced angina, and only 2
presented electrocardiographic modifications during exercise. We believe that patients with the anginal syndrome and normal coronary arteries do not have a true myocardial ischemia despite the clinical, electrocardiographic and metabolic abnormalities found during stress. The underlying mechanism of these manifestations is still unknown. The absence of ischemia could explain the good tolerance and the favorable prognosis of this clinical entity.
References 1. Kemp HG, Vokonas PS, Cohn PF, et ah The anginal syndrome associated with normal coronary angiograms. Report of a six year experience (abstr). Circulation 44:suppl 11:45, 1971 2. Neill WA, Judkins MP, Dhinsa DS, et ah Clinically suspect ischemic heart disease not corroborated by demonstrable coronary artery disease. Amer J Cardiol 29:171-179, 1972 3. Pepine CJ, Bemiller CR, Rogers A: Long-term observations in patients with angina and normal coronary arteriograms (abstr). Amer J Cardiol 29:285, 1972 4. Waxier EB, Kimbiris D, Dreifus LS: The fate of women with normal coronary arteriograms and chest pain resembling angina pectoris. Amer J Cardiol 28:25-32, 1971 5. Dwyer EM Jr, Wiener L, Cox JW: Angina pectoris in patients with normal and abnormal coronary angiograms. Hemodynamic and clinical aspects. Amer J Cardiol 23:639-646, 1969 6. Kemp H, Elliott WC, Gorlin R: The anginal syndrome with normal coronary arteriography. Trans Ass Amer PJ~ysicians 80:59-70, 1967 . 7. Neill. WA, Kassebaum DG, Judkins MP: Myocardial hypoxia as the basis for angina pectoris in a patient with normal coronary arteriograms. New Eng J Med 279:789-792, 1968 8. Hurst JW, Logue RB: The Heart, Arteries and Veins. New York, McGraw-Hill, 1970, p 671 9. Bourassa MG, Lesp~rance J, Campeau L, et ah Selective coronary angiography using a percutaneous femoral technique. Canad Med Ass J 102:170-173, 1970 10. Linhart JW: Myocardial function in coronary artery disease determined by atrial pacing. Circulation 44:203-212, 1971 11. Williams JCP, O'Donovan TPB, Wood EH: A method for calculation of areas under indicator-dilution curves. J Appl Physiol 21:695-699, 1966 12. Hohorst HJ: L (-I-) lactate: determination with lactic dehydrogenase and DPN. In, Method of Enzymatic Analysis (Bergmeyer MV, ed). New York, Academic Press, 1963, p 266 13. James TN: Angina without coronary disease. Circulation 42:189-191, 1970 14. Eliot RS, Bratt G: The paradox of myocardial ischemia and necrosis in young women with normal coronary arteriograms. Relation to abnormal hemoglobin-oxygen dissociation. Amer J Cardiol 23:633-638, 1969 15. Khaja F, Parker JO, Ledwich RJ, et al: Assessment of ventricular function in coronary artery disease by means of atrial pacing and exercise. Amer J Cardiol 26:107-116, 1970 16. Lau SH, Cohen Sl, Stein E, et ah Controlled heart rate by
17.
18. 19.
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23. 24. 25.
26. 27.
28. 29.
September 7, 1973
atrial pacing in angina pectoris: a determinant of electrocardiographic S-T depression. Circulation 38:711-720, 1968 Helfant RH, Forrester JS, Hampton JR, et ah Coronary heart disease. Differential hemodynamic, metabolic and electrocardiographic effects in subjects with and without angina pectoris during atrial pacing. Circulation 42:601610, 1970 Parker JO, Fareeduddin K, Case RB: Analysis of left ventricular function by atrial pacing. Circulation 43:241-252, 1971 Forrester JS, Helfant RH, Pasternac A, et ah Atrial pacing in coronary heart disease. Effect on hemodynamics, metabolism and coronary circulation. Amer J Cardiol 27:237-243, 1971 Bahler RC, MacLeod CA: Atrial pacing and exercise in the evaluation of patients with angina pectoris. Circulation 43:407-419, 1971 Lelghton RF, Zaron SJ, Robinson JL, et ah Effects of atrial pacing on left ventricular performance in patients with heart disease. Circulation 40:615-622, 1969 Parker JO, Ledwich JR, West RO, et ah Reversible cardiac failure during angina pectoris. Hemodynamic effects of atrial pacing in coronary artery disease. Circulation 39:745757, 1969 Ross J Jr, Unhart JW, Braunwald E: Effects of changing heart rate in man by electrical stimulation of the right atrium. Circulation 32:549-558, 1965 Friesinger GC, Likar I, Biern RO, et ah Vasoregulatory asthenia: a cause for false-positive exercise electrocardiograms (abstr). Circulation 32:supp111:90, 1965 Kannel WB, Dawber TR, Cohen ME: The electrocardiogram in neurocirculatory asthenia (anxiety neurosis or neurasthenia). A study of 203 neurocirculatory asthenia patients and 757 healthy controls in the Framingham study. Ann Intern Med 49:1351-1360, 1958 Case RB, Roselle HA, Crampton RS: Relation of S-T depression to metabolic and hemodynamic events. Card!ologia (Basel) 48:32-41, 1966 Holmgren A, Strom G: Blood lactate concentration in relation to absolute and relative work load in normal men, and in mitral stenosis, atrial septal defect and vasoregulatory asthenia. Acta Med Scand 163:185-193, 1959 Pitts FN Jr, McClure JN Jr: Lactate metabolism in anxiety neurosis. New Eng J Med 277:1329-1336, 1967 Winterscheid LC, Bruce RA, Blumberg JV, et al: Effects of isoproterenol on carbohydrate metabolism of isolated canine heart. Circ Res 12:76-84, 1963
The American Journal of CARDIOLOGY
Volume 32
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The American
Journal-of CARDIOLOGY VOLUME 32 NUMBER 3
CLINICAL STUDIES
Myocardial Function During Atrial Pacing in Patients with Angina Pectoris and Normal Coronary Arteriograms Comparison with Patients Having Significant Coronary Artery Disease
ROBERT ARBOGAST, MD, MSc* MARTIAL G. BOURASSA, MD, FACC
Montreal, Quebec
From the Montreal Heart Institute and the Department of Medicine, University of Montreal School of Medicine, Montreal, Quebec, Canada. This work was supported by research funds from the J. L. Levesque Foundation and the National Health and Welfare of Canada, Project 604-7-672. Manuscript accepted February 7, 1973. *Present address: University of California at Davis, Medical School, Section of Cardiology, Davis, Calif. 95616. Address for reprints: Martial G. Bourassa, MD, Montreal Heart Institute, 5000 East, Belanger St., Montreal 410, Quebec, Canada.
Right atrial pacing at 140 beats//min for 8 minutes induced an electrocardiographic "ischemic pattern" in 10 patients with normal coronary arteriograms and chest pain usually typical of angina pectoris (group X). The findings were compared with those in 11 patients with demonstrable coronary arterial stenosis who had the same electrocardiographic "ischemic pattern" during pacing (group C). Six patients of group X and eight patients of group C experienced angina during pacing. In addition, a low level of myocardial extraction (less than 10 percent) or production of lactate was observed during pacing in five patients of group X and in seven of group C. Patients of group X showed a significant rise in cardiac index (P <0.05) and left ventricular minute work index (P <0.01), a significant reduction in left ventricular end-diastolic pressure (P <0.01) and unchanged systemic vascular resistance. In contrast, patients of group C showed a significant lowering of cardiac index (P <0.01), unchanged left ventricular minute work index and left ventricular end-diastolic pressure and increased systemic vascular resistance (P <0.001). "Pacing ventricular function curves," obtained by plotting left ventricular stroke work index against left ventricular enddiastolic pressure, showed marked differences between the two groups. Although the clinical, electrocardiographic and metabolic manifestations were similar in both groups, the mechanism underlYing these abnormalities is probably different. Indeed, if patients with the anginal syndrome and normal coronary arteries had myocardial ischemia, they should, like patients with coronary artery disease, exhibit a depressed or unchanged rather than enhanced left ventricular function during pacing stress.
Several recent studies have stressed the paradox of patients who h a v e both angina pectoris and normal coronary arteriograms. T M These patients cannot be distinguished clinically from patients with coronary artery diseaseZ,2,5; they often show an "ischemic" electrocardiographic pattern 1,2 and, in some cases, biochemical evidence of myocardial ischemia during stress. 1,3,6,7 A previous study 5 found no
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MYOCARDIAL FUNCTION DURING ATRIAL PACING--ARBOGAST AND BOURASSA
mg, and local anesthesia. A no. 7F Cournand catheter was placed in the mid portion of the coronary sinus through an antecubital vein, and its position was verified by a small injection of contrast material. A no. 8F, type R P X 063 polyethylene catheter (Becton and Dickinson Co.) was positioned in the left ventricle by a retrograde percutaneous femoral arterial technique. A no. 6F bipolar electrode catheter (USCI) was positioned at the entry of the right atrium through a percutaneous femoral vein approach. Ten minutes after introduction of all catheters, left ventricular and aortic pressures were recorded at normal and high levels of sensitivity at recording speeds of 25 and 100 mm/sec, I0 ml of blood was sampled from the coronary sinus and ascending aorta and a dye-dilution curve was obtained by injection in the coronary sinus and sampling in the aorta at a speed of 20 ml/min with use of a calibrated Harvard pump. Then, atrial tachycardia was induced by connection of the electrode catheter to an external pacemaker (Medtronic demand model 5840). The heart rate was rapidly increased to approximately 140 beats/min, and a 12 lead electrocardiogram recorded; whenever second degree atrioventricular block developed or the duration between the R wave and the following spike induced by the pacemaker was less than 0.10 second, pacing was stopped and 0.8 m g of atropine sulfate was administered intravenously. After 2 minutes, pacing was restarted. The stimulation was adequate in all patients under these conditions. After 8 minutes of stimulation, or 5 minutes after the appearance of chest pain, the recordings and samplings were repeated. Diagnostic left ventricular cineangiograms and selective coronary arteriograms in multiple projections were then obtained as previously described. 9 Interpretation of the coronary anglograms was routinely performed by three radiologists. Significant coronary artery disease was diagnosed as any stenosis equal to or greater than 50 percent of one or more major coronary arteries.
significant differences in the h e m o d y n a m i c d a t a at rest a n d during exercise of these p a t i e n t s a n d those with d e m o n s t r a b l e coronary artery disease. This c o m m u n i c a t i o n is the first to r e p o r t the influence of a s t a n d a r d i z e d atrial pacing stress test on h e m o d y n a m i c indexes in p a t i e n t s w i t h o u t coronary artery disease b u t a definite " i s c h e m i c " electrocardiographic p a t t e r n during the test. T h e d a t a are c o m p a r e d with d a t a o b t a i n e d u n d e r the s a m e conditions in patients with coronary artery disease who h a d the s a m e clinical a n d electrocardiographic findings during pacing. Methods Patients
Ten patients with a definite electrocardiographic "ischemic" pattern during atrial pacing, angina pectoris (typical in six and atypical in {our) and normal or near normal coronary arteriograms (group X) were studied. The data were compared with those of 11 patients who had the same electrocardiographic abnormalities during pacing and who had angina pectoris (typical in eight and atypical in three) and demonstrable stenosis of one or more coronary arteries {group C). Chest pain in all patients was defined according to the criteria of Hurst and Logue. s Patients with abnormal heart sounds or murmurs, diastolic blood pressure greater than 100 mm Hg, clinical evidence of cardiac failure or abnormal heart size on X-ray examination, abnormal S - T segment on the resting electrocardiogram or recent intake of digitalis and beta blocking agents were excluded. Investigative Procedure
All patients were studied in the fasting state after premedication with meperidine, 50 mg, and phenergan, 25 @ TABLE I
Values Obtained at Rest and During Atrial Pacing in Patients of Both Groups (means ± standard error of the mean)
Sex
Age (yr)
Condition
HR
AoP
TTI
LVEDP
Cl
TPR
LVMWI
LVSWI
LVSPI
4834 ±564 6104 ±508 +1269 ±384
61.6 ±5.01 43.0 ±3.46 --18.6 ±3.09
214 ±19 210 ±16 --3.6 ±11.0
4699 ±478 4508 ±294 --191 ±279
60.1 ±4.81 31.1 ±2.08 --29.0 ±3.44
201 ±16 158 ±13 --42.7
Group X (Angina Pectoriswith Normal CoronaryArteriogram) (no. = 10) M 4; F6
37 ±1.9
Rest Pacing A
78 ±5.0 141 ±1.5 .1.67 ±2.9
95.9 ±4.63 106.4 ±4.42 +10.5 ±3.31
2390 ±164 3289 ±155 ,1,899 ±168
9 ±0.86 3.5 ±0.58 --5.5 ±0.50
3.62 ±0.35 4.06 ±0.30 +0.44 ±0.19
1395 ±122 1356 ±110 --39.5 ±34.4
Group C (Angina Pectoriswith CoronaryStenosis)(no. = 11) M 11; F0
48 ±2.1
Rest Pacing
78 ±3.5 145 ±2.2 .1.63 ±4.9
93.8 ±5.19 107.7 ±4.30 .1.13.9 ±4.0
2475 ±221 3356 ±198 .1.880 =1=196
10.55 ±0.78 12.82 ±1.87 ,1,2.27 ±1.86
3.59 ±0.27 3.28 ±0.29 --0.32 ±0.09
1182 ±90 1561 ±157 .1.379 ±93
±11.3
AoP = mean aortic pressure (mm Hg); CI = cardiac index (liters/min per m=); HR = heart rate (beats/min); LVEDP = left ventricular end-diastolic pressure (mm Hg); LVMWl ---- left ventricular minute work index (g-m/min per m2); LVSPI = left ventricular stroke power index (g-m/sec per m2); LVSWl ----left ventricular stroke work index (g-m/systole per m2); TPR = total peripheral resistance (dynes sec cm-s); TTI ----tension-time index (mm Hg sec/min). A ----mean difference between values obtained at rest and during pacing.
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MYOCARDIAL FUNCTION DURING ATRIAL PACING--ARBOGAST AND BOURASSA
The pressures were recorded through a fluid-filled left ventricular catheter directly connected to a S t a t h a m P23Db strain gauge on a photographic r e c o r d e r (Honeywell Visocorder oscillograph model 1612). All pressure determinations were averaged over 10 consecutive beats. Left ventricular end-diastolic pressure was measured at the coincidence point of the downslope of the ventricular a wave and the initial left ventricular pressure upstroke. During pacing-induced tachycardia, this point could not be determined in some cases; in the latter,-we measured the lowest point before the initial left ventricular pressure upstroke which occurs very near the peak Of the R wave of the electrocardiogram (lead II), as reported by others. 1° M e a n aortic pressure was d e t e r m i n e d electronically. M e a n aortic systolic pressure was calculated by p l a n i m e t r y of the area between the onset of the pressure upstroke a n d the trough of the dicrotic notch according to the formula: M e a n aortic systolic pressure = s -1 f o P(t) dt, where s is the ejection time and P the pressure at instant t. Cardiac output was d e t e r m i n e d by the dye-dilution technique, and the area under the dye curve was calculated according to the method of W i l l i a m s et al. 11 Injection of dye was performed with a precision syringe (BD Cornwall Luer-lok) in order to inject exactly the same a m o u n t of dye during each period. A standard 12 lead electrocardiogram was recorded at rest and every 30 seconds during atrial pacing on a conventional electrocardiograph (Hewlett-Packard a u t o m a t i c cardiograph model 1513 A). T h e criteria for a positive "ischemic" p a t t e r n were a straight S - T segment depression of 1 m m (0.1 mv) or more, with a m i n i m a l duration of 0.08 second and a horizontal or descending slope in any lead during atrial pacing. Lactate determinations were performed in duplicate according to the e n z y m a t i c method of Hohorst. 12 A variation coefficient ( s t a n d a r d d e v i a t i o n / m e a n × 100) of 5.14 percent was found with this technique in our laboratory using 26 s t a n d a r d samples. M y o c a r d i a l extraction was cal-
TABLE II Summary of the HemodynamicResults Difference Between Restand Pacing
Heart rate Mean aortic pressure Tension-time i n d e x Left ventricular end-diastolic pressure Cardiac i n d e x Total peripheral resistance Left ventricular minute work index Left: ventricular stroke work index Left ventricular stroke power i n d e x
Difference
GroupX
Group C
Between Groups
t *** t * ~' * * * ,~ * * *
~ *** t ** t*** NS
NS NS NS ***
t * NS
~ ** t ***
*** ***
t **
NS
**
~ ***
~ ***
*
NS
~ **
*
NS = not significant; * = P <0.05; * * = P <0.01; * * * = P <0.001; t = significant increase during pacing; $ = significant decrease during pacing.
AoP I (mm Hg) 140
GROUP X
GROUP C
t =3.17
t =3.48
P < 0.025
p < 0.01
orest ~
130
i meanPaCing
120
+S.EM
IO0
9O 80 7O Z~AoP +20 J-
t< 1
.16 I-
N.S.
~TE
+12~
FIGURE 1. Values of mean aortic pressure (AoP) obtained at rest and during pacing in the two groups of patients. ~AoP = mean difference between values at rest and during pacing; N.S. = not significant; p = probability; S.E.M. = standard error of the mean.
culated by the equation: Extraction (%) = (value in aorta - value in coronary sinus)/value in aorta × 100. The following formulas were used in the calculations:. Total peripheral resistance (dynes sec cm -5) = mean aortic pressure x 1,332/cardiac output (liters/rain) × 103/60. ( . Tension-time index (ram Hg sec per mln) = mean aortic systolic pressure × ejection time (seconds) x heart rate (beats/rain). Left ventricular minute work index ( g - m / m i n per m 2) = (mean aortic systolic pressure - left ventricular enddiastolic pressure) x cardiac index (liters/rain per m 2) x 13.6. Left ventricular stroke work index (g-m/systole per m 2) = left ventricular minute work i n d e x / h e a r t rate. Left ventricular stroke power index (g-m/sec per m 2) = left ventricular minute work index/injection time. All calculations were performed with a Hewlett-Packard model 9100-A calculator using the same program. S t a t i s t i c a l a n a l y s i s : The difference between hemodynamic indexes obtained at rest and during pacing was tested against zero using a t test for paired data. For each index, the difference between the two periods was calculated and expressed as 4. The A value obtained was compared between groups by a t test for grouped data.
Results D u r i n g p a c i n g , a n g i n a p e c t o r i s o c c u r r e d in six p a t i e n t s of g r o u p X ( a n g i n a p e c t o r i s w i t h n o r m a l a r t e r i o g r a m ) a n d e i g h t p a t i e n t s of g r o u p C ( a n g i n a p e c toris with coronary stenosis). All hemodynamic findings a r e s u m m a r i z e d i n T a b l e s I a n d II. Heart rate: Heart rates at rest and during pacing a n d t h e i n c r e m e n t i n d u c e d b y p a c i n g were n o t significantly different between groups.
September7, 1973 The AmericanJournalof CARDIOLOGY Volume32
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MYOCARDIAL FUNCTION DURING ATRIAL PACING--ARBOGAST AND BOURASSA
TTI
GROUP X
GROUP C
(mmHg. sec/min)
t=5.34
t =4.48
p< 0.001
p
• 4400
LVEDP
GROUP X
(ram Hg)
t=-11.00
t=1.22
p < 0.001
N.S.
25
o rest
4000'
GROUP C
o rest
• pacing mean
3600
• pacing
20-
"~-+S.E.M
3200
15
2800
10
Q,
2400 5 2000 LVEDP
1600 ATT/1200 :
t =3.86
+6.+4
l
t
p < 0.001
+2 0 -2 + 400 F
--4=
i
0FIGURE 2. Values of tension-time index (TTI) obtained at rest and during pacing in the two groups of patients. ATTI = mean difference between values at rest and during pacing.
Mean aortic pressure: This value increased significantly in both groups during pacing; however, the increment was not different between goups (Fig. 1). Tension-time index: Pacing induced a highly significant and similar increase of tension-time index in both groups (Fig. 2). Left ventricular end-diastolic pressure: During atrial pacing, left ventricular end-diastolic pressure
CI (i/min/m2) 7
GROUP X
GROUP C
t =2.27 p<0.05
t=-3.63 p< 0.005
6 FIGURE 3. Values of left ventricular end-diastolic pressure (LVEDP) obtained at rest and during pacing in the two groups of patients. ~ L V E D P = mean difference between values at rest and during pacing.
decreased significantly in group X (P <0.001) but was not significantly changed in group C. The variation of left ventricular end-diastolic pressure (A) induced by pacing was significantly different between groups (P <0.001) (Fig. 3). Cardiac index: This index was significantly altered in both groups, increasing in group X (P <0.05) and decreasing in group C (P <0.01). The
GROUP X o rest
(dynesT.Ps~c.cm.5) 220^~
°F
• pacing
GROUP C
t=-l.15
l= 4.06
I
N.S.
p< 0.001
I
ooo -
,oo1-
//
//
I °re,'
I
1600
2 1 ~Cl
. 0 . 6 I+0.41-
t=3.69
p < 0.001 ATPR [+300~
-0.2~ -0.4 -0.6
•,oo
p <0.001
N
-lOOp
FIGURE 4. Values obtained at rest and during pacing for cardiac index (CI) in liters per minute per square meter body surface area. ACh = mean difference between values at rest and during pacing.
FIGURE 5. Values obtained at rest and during pacing for total peripheral resistances (TPR). ATPR = mean difference between values at rest and during pacing.
260
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The A m e r i c a n Journal of C A R D I O L O G Y
MYOCARDIAL FUNCTION DURING ATRIAL PACING--ARBOGAST AND BOURASSA '
® 2000 group ~ ~
1500-
".,,
• LVSWI '(g.m/sys.t./m2) 70
A LVMWI (g-m/min/m 2)
} mean -+S.EM
o group X
• group C
60
100050
"-.500
,/"
\
\
-
40 l÷"
""-I I ,2t ,3 4, ,~ ,6 ~tvEDP (ram Hg) •
"
I"
oroop
p< 0.01
~z
30
C
FIGURE 6. Plotting of changes of left ventricular minute work index (ALVMWI) against changes of left ventricular end-diastolic pressure (ALVEDP) induced by atrial pacing in the two groups of patients.
variation of cardiac index was significantly different between groups (P <0.001) (Fig. 4). Total peripheral resistance: A significant variation was found only in group C (P <0.001). This variation was significantly different between groups (P <0.001) (Fig. 5). Left v e n t r i c u l a r w o r k indexes: Left ventricular minute work index was unaffected by pacing in group C and was increased in group X (P <0.01). When the change in left ventricular minute work index (A) is plotted against the change in left ventricular end-diastolic pressure, the variation of left ventricular minute work index is clearly different between groups (Fig. 6). Left ventricular stroke work index, although significantly lowered in both groups during pacing (P <0.001), was less modified in group X (P <0.05) and was significantly higher in this group during pacing (P <0.01). "Pacing ventricular function curves" were obtained by plotting left ventricular stroke work index against left ventricular end-diastolic pressure. For each patient, the line between rest and pacing values forms an angle (~) with the abscissa. This angle was calculated by the following equation: Tangent a = A left ventricular stroke work index/A left ventricular end-diastolic pressure or a = arch tangent of (A left ventricular stroke work index/A left ventricular end-diastolic pressure), where arch tangent is the inverse function of tangent. The mean values expressed in degrees (4- standard error of the mean) were 65.2 (±3.9) and 93.6 (4-4.1) in groups X and C, respectively. The difference between the groups was highly significant (P <0.001) (Fig. 7). Left ventricular stroke power index was not affected by pacing in group X but decreased significantly in group C (P <0.01) (Fig. 8). Myocardial lactate extraction: In both groups, myocardial lactate extraction was reversed to production during pacing in some patients (three of group X and four of group C). A low level of extraction (less than 10 percent) or production was observed during pacing in five patients of group X and in seven of group C (Fig. 9).
I I
I
2
4
I
I
I
I
I
I
6 8 10 12 14 16 LVEDP (mm Hg) F I G U R E 7. "Pacing ventricular function curves" obtained by plotting mean values of left ventricular stroke work index (LVSWI) against mean values of left ventricular end-diastolic pressure (LVEDP). The slopes of the curves or the angles which form these slopes with the abscissa for the two groups of patients are significantly different (P <0.001) (see text for explanation). Mean values of left ventricular stroke work index obtained during pacing are significantly different between the two groups (P <0.01).
Effect of administration of atropine: For all variables, there was no significant difference among patients who did and did not receive atropine when all patients or patients in the two groups were considered separately. Discussion
~'
In patients with normal coronary arteries, three
possible mechanisms have been suggested for the occurrence of angina pectoris: 13 (1) an abnormal affinity of hemoglobin for oxygenZ~; (2) occlusive disease
LVSPI (g.m/sec/m2)
350i
GROUP X t=-0.33
N.S.
GROUP C t =-3.79 p < 0.005 o rest
• pacing
F
10%17 A LVSPI
"b
t = 2.47 p < 0.025
-20 I -40
-60 FIGURE 8. Values obtained at rest and during pacing for left ventricular stroke power index (LVSPI). ALVSPI = mean difference between values at rest and during pacing.
S e p t e m b e r 7, 1 9 7 3
The A m e r i c a n Journal of C A R D I O L O G Y
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MYOCARDIAL FUNCTION DURING ATRIAL PACING--ARBOGAST AND BOURASSA
LACTATE
60
--
GROUPX
GROUP C
'40 %extraction 20
1o 0 2O
% produclion 40
:;=,ng
60-FIGURE 9. Values obtained at rest and during atrial pacing for myocardial lactate extraction or production.
of small coronary vessels; and (3) failure of the technique of coronary angiography to detect significant stenosis in the major coronary arteries. All these hypotheses postulate a common underlying mechanism: myocardial ischemia as observed in coronary artery disease. There are some discrepancies in natural history between patients with angina pectoris secondary to coronary atherosclerosis and patients with the anginal syndrome and normal coronary arteries. The prognosis tends to be benign in patients without visualized coronary arterial stenosis, and gradual clinical improvement will occur in more than half of these patients during long-term follow-up studies. 1,4 Sudden death and myocardial infarction are probably rare. In the reported cases, small and large coronary arteries were free of disease, and histologic evidence of myocardial necrosis was often absent or localized in the subendocardial layers. ~,1. To our knowledge, myocardial damage leading to chronic cardiac failure has never been reported in such patients. It is therefore conceivable that a metabolic abnormality, perhaps transient, rather than an irreversible anatomic lesion could account for the manifestations observed in these patients. In this study, we attempted to determine--using the same objective index of myocardial "ischemia": namely, electrocardiographic "ischemic" modificat i o n s - w h e t h e r patients with chest pain suggestive of angina pectoris with or without visualized coronary artery disease have the same myocardial functional response during atrial pacing. If true hypoxia occurred in both categories of patients, a similar decrease in myocardial performance should be expected. 1~ Electrocardiographic modifications were used as the criteria for inclusion in the study rather than occurrence of angina in order to avoid the suggestive bias associated with the assessment of angina. In fact, it has been observed in patients with coronary artery disease that pain, "ischemic" electrocardiographic modifications and abnormal myocardial performance ~°,~6,~7 are not necessarily present together. The usefulness of atrial pacing in the assessment of myocardial function in patients with coronary ar262
September 7, 1973
The American Journal of CARDIOLOGY
tery disease has been documented recently. 1°,1s,19 We used a standardized stress test (heart rate abruptly increased to 140 beats/min) in order to study all patients under similar conditions. We have therefore obtained comparable levels of heart rate and tension-time index, predicting comparable levels of myocardial oxygen requirements. The induced heart rate was generally higher than in previous studies, and pacing was always maintained for at least 5 minutes; this technique was preferred to use of short periods of pacing up to the anginal threshold because it has been postulated that relatively long ischemic periods may be necessary to induce ventricular dysfunction. 2° Mechanism of S-T changes and angina pectoris in absence of coronary disease: Most of the hemodynamic changes induced by pacing were significantly different in the two groups of patients (Table II). Mean arterial pressure increased in both groups, a finding noted by others, l°,21 The large decrease in left ventricular end-diastolic pressure during pacing in the group with normal coronary arteriograms (group X) was similar to that seen in normal subjects, whereas considerable individual variations were observed in the patients with coronary artery disease. 1°,17,18,2°,22 Cardiac index, as described by others, 1~ can be lowered in patients with coronary artery disease; however, the decline is not usual, and was probably secondary in our patients to the different technique of pacing stress. In contrast, at a similar heart rate and with the same electrocardiographic modifications, patients of group X had an elevated cardiac index. This finding has never been reported in normal subjects. '28 Despite the higher cardiac index, total peripheral resistance was unchanged, in contrast to findings in the group with coronary artery disease. In addition, pacing ventricular function curves showed marked differences between the two groups. Therefore, we can postulate that the mechanism inducing electrocardiographic modifications in all and angina pectoris in six of the patients of group X is probably not myocardial ischemia. This assertion seems to conflict with the observed electrocardiographic and metabolic modifications. However, both manifestations have been observed in subjects with neurocirculatory asthenia or anxiety neurosis which recently have been suggested to be related to the syndromes observed in our patients. 4 Electrocardiographic modifications of the "ischemic" type have commonly been observed in neurocirculatory asthenia. 24,25 In addition, S - T segment depression is more closely related to metabolic abnormalities than hypoxia itself. 26 Similarly, a relatively greater production of lactate in the peripheral circulation during exercise has been observed in patients with these syndromes. 27 The causative role of increased levels of circulating catecholamines has been suggested. 2s Myocardial lactate production has not been documented in such patients, but experimental data in dogs have shown that during an increase in cardiac metabolic rate induced by isoproterenol, lactate is being excreted rather than utilized. 29 The presence of "ischemic" electrocardiographic modifiVolume 32
MYOCARDIAL FUNCTION DURING ATRIAL PACINGmARBOGAST AND BOURASSA
cations and myocardial lactate production is therefore not necessarily in conflict with the enhanced myocardial performance incompatible with true myocardial ischemia. The discrepancy between our results during pacing and the hemodynamic data previously reported 5 during exercise is unexplained. Pacing is probably a more specific stress for the heart than exercise, which also involves the peripheral circulation, is In addition, the group of patients previously described5 may not have been comparable to our patients; only
3 of these 10 patients experienced angina, and only 2
presented electrocardiographic modifications during exercise. We believe that patients with the anginal syndrome and normal coronary arteries do not have a true myocardial ischemia despite the clinical, electrocardiographic and metabolic abnormalities found during stress. The underlying mechanism of these manifestations is still unknown. The absence of ischemia could explain the good tolerance and the favorable prognosis of this clinical entity.
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The American Journal of CARDIOLOGY
Volume 32
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