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Use of QRS scoring and thallium-201 scintigraphy to assess left ventricular function after myocardial infarction
Use of QRS Scoring and Thallium-201 Scintigraphyto Assess Left Ventricular FunctionAfter Myocardial Infarction NICHOLAS L. DePACE, MD, ABDULMASSIH S. ISKANDRIAN, MD, A-HAMID HAKKI, MD, SALLY A. KANE, RN, and BERNARD L. SEGAL, MD
To determine the usefulness of the QRS scoring system in predicting left ventricular function, and the correlation between the QRS score, left ventricular ejection fraction, and the size of infarction, patients with acute or chronic infarction were studied by means of 12-lead electrocardiography, rest thallium-201 scintigraphy, and radionuclide angiography. In patients with acute infarction there was a statistically significant correlation between the QRS score and the left ventricular ejection fraction (n = 28, r = -0.81, p
with chronic infarction before they underwent coronary artery bypass, there was still a fair correlation between thallium score and left ventricular ejection fraction (n = 15, r = 0.61, p <0.02) but not between thallium score and QRS score (r = 0.03, p >0.05). In addition, in these patients with chronic infarction who underwent coronary revascularization, there was still a fair correlation between the postoperative thallium score and the postoperative left ventricular ejection fraction (r = 0.75, pO.OS) or between the yo:;yre and the ejection fraction (r = 0.24, p
Left ventricular performance is an important factor in determining prognosis in patients with chronic coronary heart disease as well as after acute myocardial infarction.‘-” Techniques that have been used as prognostic indicators after acute infarction include evaluation of left ventricular ejection fraction and wall motion by radionuclide angiography’j and evaluation of the size of the scarred or ischemic myocardium by rest thallium-
201 scintigraphy.7 In addition, a specific appearance of the technetium-99m pyrophosphate images has been correlated with poor prognosis.8 Finally, exercise testing with or without thallium-201 imaging or radionuclide ventriculography has been used to categorize patients after acute infarction in different risk groups.9310 Recently, Palmeri et al,l’ using a QRS scoring system, were able to evaluate left ventricular function in patients with acute myocardial infarction. The QRS scoring system was still fairly accurate in predicting ventricular function up to 1 year after acute infarction in the group of patients they followed up. We were intrigued by the fact that a QRS score would work at all. If it does, then it is probably due to electrical
From the Likoff Cardiovascular Institute of Hahnemann Medical College and Hospital, Philadelphia, Pennsylvania. Manuscript received March 29, 1982; revised mariuscript received May 27, 1982, accepted June 16, 1982. Address for reprints: Abdulmassih S. Iskandrian, MD, Likoff Cardiovascular Institute, Hahnemann Medical College and Hospital, 280 North Broad Street, Philadelphia, Pennsylvania 19102.
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The size of the defect appears related to the left ventricular ejection fraction in both patients with acute infarction and those with chronic infarction. The QRS scoring system in patients with acute infarction and the size of the thallium defect in patients with acute or chronic infarction can categorize patients into those who have a low, moderate, and normal ejection fraction.
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forces from viable myocardium. The other noninvasive way to demonstrate viable myocardium is thallium-201 imaging. Furthermore, if there is a change in left ventricular ejection fraction as a result of improvement in myocardial flow by coronary artery bypass surgery, a change of QRS score might be expected as well and probably an improvement in the thallium perfusion defect. The purpose of this study was to compare the usefulness of the QRS scoring system of la-lead electrocardiograms with that of resting thallium-201 scintigrams in evaluating the left ventricular function of patients with acute or old myocardial infarction before and after coronary artery bypass.
TABLE I
ET AL
Criteria for Determining Point Score in the QRS Scoring System
Criteria (Number of Points) -
V4
0 130 ms (1) Q 240 ms (2) QZ30ms(l) Q 230 ms (1) Q 250 ms i3j Q 140 ms (2) Q 230 ms (1) Anv Q (1) R 250 &IS (2) R L40ms(l) AnyQorR120ms(l) R 260 ms (2) R 250 ms 111 Any Q or k’i30 Q 220 ms (1)
v5
Q 230 ms (1)
V6
Q 130
I, aVL aVF V,
v2
V3
Amplitude
Duration
Lead
Methods We studied 2 groups of’patients. The first group consisted of 37 patients with the diagnosis of acute infarction confirmed by typical history, electrocardiographic changes, and elevation in serum enzyme and specific cardiac isoenzyme levels. These patients were admitted to the coronary care unit over a 2month period. Thallium-201 images at rest are obtained in most patients with acute infarction admitted to our coronary care unit. The second group consisted of 43 patients with a documented history of myocardial infarction (more than 3 months before hospit,alization) as determined by history, electrocardiography, and cardiac enzyme levels. Sixteen of the 43 patients subsequently underwent coronary bypass because of angina pectoris. Standard 12-lead surface electrocardiograms were obtained with a 3-channel Hewlett-Packard recorder at a paper speed of 25 mm/s daily for 3 days and as clinically indicated afterward in 37 patients with acute myocardial infarction. If left ventricular hypertrophy, left anterior hemiblock (QRS axis Z-60”), right or left bundle branch block, ventricular preexcitation, or nonspecific intraventricular delay (QRS L 110 ms) was present on the electrocardiogram at 2 weeks, the patient was withdrawn from the study because the QRS score does not work in these patients. Using these exclusion criteria, we withdrew 8 patients from the study; therefore, 29 patients comprised the study group. Follow-up electrocardiograms were obtained at 2 weeks and compared with radionuclide angiograms performed at that time. Thallium-201 scintigraphy was performed at rest in 22 of the 29 patients 2 weeks after infarction as well. In the remaining 7 patients, thallium images were not obtained because either the pat,ient or the treating physician refused t,he studies. A transmural infarct was considered anterior or inferior when new Q waves 230 ms were present in the precordial leads or lead aVF, respectively. A non-Q-wave infarct was diagnosed when patients had a typical history of infarction with appropriate enzyme elevation, but in whom a Q wave 230 ms did not develop in the electrocardiogram. The QRS scoring system was based on the system developed by Selvester et al.l’.l:l Q- and R-wave durations and R/Q and R/S amplitudes and ratios in 10 of 12 standard electrocardiographic leads were analyzed (Table I). QRS scores could range from a minimal value of 0 to a theoretical maximum of 29 points. In patients with chronic infarction, radionuclide angiograms were not available soon after acute infarction. Each patient, however, subsequently underwent electrocardiography and radionuclide angiography. These patients were consecutive patients being evaluated in the nuclear cardiology laboratories for symptoms of angina pectoris. Sixteen of the 43 patients
FUNCTION-DePACE
Reproduced the American
ms (1)
R/Q
Ratio
51 (1)
; 2
R/Q 51 (1) R/Q I1 i2j
ms (1)
R/Q
52 (1)
R/S
L 1 (1)
R/S
21.5
R/Q R/Q R/Q R/Q R/Q R/Q
or or or or or or
R/S R/S R/S R/S R/S R/S
Maximal Points
(Ir 10.5 I1 I1 12 I1 53
from Wagner et all3 with permission Heart Association.
(2) (1) (2) (1) (2) (1)
l 3 3
of the authors and
subsequently underwent coronary artery bypass surgery. In 15 of the 16 patients, thallium-201 images at rest were also available preoperatively. Ten to 14 days after surgery, electrocardiography, thallium-201 imaging at rest, and radionuelide angiography at rest were repeated in all but 1 of these 15 patients. Radionuclide angiography at rest was performed by means of a first-pass technique with a computerized multicrystal gamma camera (Baird-Atomic Systems-77) equipped with a l-inch (2.54 cm) parallel-hole collimator positioned anterior to the precordium. The study was inadequate in 1 patient because of a poor bolus injection. The technique for measuring the ejection fraction has been described in detail from thisI and other 1aboratories.l” In a previous study we showed an excellent correlation between radionuclide-derived ejection fractions and similar measurements obtained during cardiac catheterization.‘4 The technique for thallium imaging was previously described in reports from this laboratory. 1Rm~0 Quantitative analysis of the thallium images was performed by the perimetric method, as previously described from this laborat,ory.‘sl’” The size of the thallium-201 defect was determined by measuring the perimeter with a computerized Hewlett-Packard 982A digitizer and expressing it as a percentage of the total left ventricular perimeter in each projection (Fig. 1). The region of the valve was excluded. This method is similar t,o that used by Field et al:’ in assessing the extent of akinetic-dyskinetic segments by means of left ventriculography. The percentage of the average abnormal perimeter was determined from 3 projections. We also assessed the thallium scans by a scoring system. The image in each of the 3 projections was divided into 3 segments. Each segment was subjectively scored as follows: a score of 0 indicated minimal or no uptake; a score of 1 indicated severe reduction in uptake; a score of 2 indicated a moderate (but definite) reduction in uptake; a score of 3 indicated a mild (thus equivocal) reduction in uptake; and, finally, a score of 4 indicated normal uptake. Because the apex of the left ventricle usually has less thallium uptake than the remaining segments, presumably because the apex is thinner than the rest of the myocardium, we multiplied the score in
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QRS SCORE
FUNCTION-OePACE
I
= 6
--4,n--
ET AL
II
- /“‘,v_ t v3
LV-EF
L
F
v,
_-.sn.A.-....A?
v4
V5
-d”_.Jv6
= 30%
Anterior
% Abnormal Perimeter Thallium Score
60 13
17 15
the remaining segments by 2, yielding a score of 20 in each projection for a total score of 60 in 3 projections (Fig. 1). However, the results were not different even when a score of 4 was used for each segment. Therefore, a score of 40 would indicate that only two thirds of the left ventricle has normal uptake. Interpretations of the electrocardiogram, radionuclide angiograms, and thallium images were made independently without knowledge of the other results. The inter- and intraobserver variability in measuring the left ventricular ejection fraction was 2.2 f 1.5%i4 and the interobserver variability in measuring the thallium defects was 4 f 4%; the maximal difference was 14% in a patient with large defects whereas the intraobserver variability in measuring the thallium defects was 3 f 3%.18J9 The intraobserver variability in measuring the QRS score was 2 f 2% with a maximal difference of 5%. Statistical analysis was performed using Student’s t test or analysis of variance when appropriate. Values were expressed as the mean f standard deviation (SD) when indicated. A probability (p) value less than 0.05 was considered to represent a statistically significant difference. Correlation between the variables was assessed with linear regression analysis. Acute myocardial infarction: Of the 29 patients with acute infarction, the infarction was transmural (Q-wave infarction) in 20 patients: anterior in 9, inferior in 6, and both anterior and inferior in 5. The remaining 9 patients had non-Q-wave infarctions (nontransmural or subendocardial). There were 23 men and 6 women with an age range of 36 to 86 years (mean 61.2).
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FIGURE 1. The QRS score, left ventricular (LV) radionuclide angiogram, and the thallium-20’ images from a patient with acute anterior infarction. EF = ejection fraction; LAO = left anterior oblique projection.
QRS scoring: Seven of the 29 patients (24%) had a QRS score of 2 or less. All 7 patients had non-Q-wave infarctions. In the remaining patients the QRS score varied between 3 and 18. Patients with transmural infarctions had higher scores than patients with non-Q-wave infarctions (8.3 f 3.8 versus 1.6 f 1.2, p
ejection fraction and QRS score in the 28 patients with acute infarction in whom both studies were available (r = -0.61, y
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ET AL
65 60 \
60
50 ; z .E p” m E t 2 B
50
40
40 30 30
20
20 IO IO 0 c 30
35
40
45
Thallium
50
55
= 45 - 1.97x, p2 had an ejection fraction 240% (p (0.01). In general, the higher the score, the lower the ejection fraction. Patients with a QRS score L 10 had an ejection fraction of 30% or less. Correlation between thallium-201 scintigrams and left ventricular function: As mentioned earlier, there was good agreement between the perimetric and scoring systems for evaluation of thallium scintigrams. We found a fair correlation between the size of the defect and the left ventricular ejection fraction (r = -0.71, y = 51.3 - 0.57x, p
50.
g40. w I 30. 5 20.
r
30
1
35
40
45
Thallium
50
55
4
6
6
IO
I2
I4
I6
I8
_QRS Score
60
Score
FIGURE 2. Comparison between thallium score and thallium percentage (abnormal perimeter) in 22 patients with acute myocardial infarction (Ml). Ant = anterior; inf = inferior.
I;[
1 2
GO
Score
FIGURE4. Comparison between the thallium score and left ventricular ejection fraction (LV-EF) in 21 patients with acute myocardial infarction. Abbreviations as in Figure 2.
FIGURE3. Comparison between QRS score and left ventricular ejection fraction (LV-EF) in 28 patients with acute infarction. Abbreviations as in Figure 2.
(Fig. 4). Patients with small defects had higher ejection fractions than patients with larger defects. All 6 patients with a thallium score 140 had an ejection fraction 125%, whereas only 2 of 15 patients (13%) with a thallium score >40% had an ejection fraction <25% (p40%, 15 of 32 patients (47%) with a QRS score >2 also had an ejection fraction >40% (p not significant). As indicated, 16 of these patients subsequently underwent’ coronary artery bypass. Resting thallium-201 scintigrams were available in 15 of the 16 patients preoperatively. Furthermore, 14 of these 15 patients had resting thallium scans 10 to 14 days postoperatively as well. The group of patients that underwent
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18
.
FUNCTION
DePACE ET At
.
16
n r
2h35 0.42x
25.3 DXO.001
Y
g0 Thallium
5’5
6’0
Score
FIGURE 5. Comparison between QRS score and thallium score in 22 patients with acute myocardial infarction. Abbreviations as in Figure 2.
surgery consisted of 14 men and 2 women, aged 41 to 69 years. Eight of the 16 patients had transmural inferior infarctions, 3 had transmural anterior infarctions, 1 had both anterior and inferior infarction, 2 had non-Q-wave infarction, and 2 had bundle branch block. The ejection fraction measured in 15 patients increased from 34 f 8% preoperatively to 38 f 12% postoperatively (0.05
0
2
4
6
8
IO
12
14
16
I6
QRS Score FIGURE 6. Comparison between QRS score and left ventricular ejection fraction (LV-EF) in 41 patients with chronic myocardial infarction. Abbreviations as in Figure 2.
was observed in the correlation between the ejection fraction and the QRS score in patients with chronic myocardial infarction, the correlation was marginal (r = -0.51). More important, careful analysis of Figures 3 and 6 shows that for any given score the ejection fraction varied widely in patients with chronic infarction but not in patients with acute infarction. These results are similar in some respects to those of Palmeri et al” but also show some differences. First, these investigators followed the same cohort of patients with acute infarction over 2 years. However, we studied entirely different groups of patients, 1 with acute infarction and 1 with
Discussion The results of this study show that in patients with acute infarction, the QRS scoring system of Wagner et all” is reliable in predicting left ventricular function. Our study, therefore, confirms the conclusion of Palmeri et al,” although our correlation was lower than that reported by these investigators (r = -0.61 versus -0.88). It is worth emphasizing that the QRS scoring system cannot be used in patients with conduction defects, but can be used whether the myocardial infarction is transmural or nontransmural (non-Q-wave infarction). Although we studied a small group of patients with acute infarction, nevertheless these patients had a wide range of left ventricular function, QRS scores, and thallium scores and therefore these observations are likely to represent findings occurring more generally in other patients with acute infarction. Although a trend
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I
I
25
30
35
40
Thallium
I
45
50
55
60
Score
FIGURE 7. Comparison between thallium score and left ventricular ejection fraction (LV-EF) before and after coronary artery bypass surgery. Postop. = postoperative; preop. = preoperative.
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chronic infarction. This difference in method is related to the design of the study-prospective in the case of Palmeri et all’ and retrospective in our study. Second, even in the study of Palmeri et al,ll the correlation between the QRS score and the ejection fraction was lower at 1 year than the correlation 2 weeks after acute infarction. The exact reasons for the poorer correlation in patients with chronic infarction in both studies are not exactly known, but certain mechanisms can be postulated: for example, the disappearance of Q waves, a compensatory increase in the end-diastolic volume, and the effects of medications that may alter preload, afterload, and contractility. Finally, the presence or absence of myocardial &hernia at rest cannot be discounted. It appears that the common denominator between the QRS score and the left ventricular ejection fraction is the amount of infarcted myocardium. A significant correlation between the extent of myocardial fibrosis and left ventricular function has been shown.“l The extent of thallium defect has been shown to correlate with pathologically determined infarct size and with the contrast angiographic extent of asynergy.2”,“:J We studied the extent of the infarcted myocardium in patients with acute infarction by means of thallium-201 scintigraphy at rest, and in fact found a fair correlation between the size of the perfusion defect, the ejection fraction, and the QRS score (Fig. 3 and 4). We also found that in patients with chronic infarction, the correlation between the size of the defect and the ejection fraction was still fair, but again we found a poor correlation between the QRS score and the size of the thallium defect in patients with chronic infarction. In addition to fibrosis, resting thallium defects may represent chronic ischemia (or hypoperfusion). These perfusion abnormalities may be responsible for the segmental left ventricular wall-motion abnormalities seen in patients with chronic coronary artery disease in the absence of infarction: they may also explain the reversibility of these wall-motion abnormalities with nitroglycerin.24 This assumption needs further study. In the subgroup of patients with chronic infarction who underwent revascularization, the postoperative correlation between the ejection fraction and the size of the thallium defect was still fair (Fig. 7). However, as in the preoperative study, the correlation between the QRS score and the thallium score, or between the QRS score and the ejection fraction was poor. These results suggest that factors inherent in the QRS scoring system may be responsible for the poor correlation between the ejection fraction and the QRS score in patients with chronic infarction. Our method for assessing the defect size seen on thallium scans is simple and may be performed in any laboratory. Moreover, the good correlation between a thallium scoring system and the perimetric method used in this study indicates that the scoring system may be preferred because of its simplicity. As noted earlier, the correlation between the 2 methods is not unexpected
FUNCTION-DePACE
ET AL
because both sets of data were derived from the same images. The ultimate validation of either method has to be made by a comparison with postmortem infarct size and probably with the contrast angiographic extent of asynergy as determined by other investigators.22,23 However, neither postmortem nor contrast angiographic data were available in our patients. Even the defect size in the thallium scans did not correlate perfectly with the left, ventricular ejection fraction (r = 0.70). There may be several related factors. First, some defects seen in the resting scans may represent ischemia (hypoperfusion) rather than scarring. Although it is our practice to obtain 4-hour delayed images after the initial resting images, the size of the defect as reported in this study represents the total defect size of both infarcted and possibly ischemic myocardium. Second, the left ventricular ejection fraction may have been affected by factors that modify the preload, afterload, and contractility.“” Third, as demonstrated in 2 patients with a small thallium defect in this study, the ejection fraction was disproportionately low compared with the size of the defect. In these patients an independent cardiomyopathic process may have been responsible for lowering the ejection fraction. It is well known that patients with nonischemic cardiomyopathy may have very low ejection fractions despite the presence of normal or near-normal left ventricular function26 (Fig. 4 and 7). Clinical implications: This study confirms a previous report that the QRS scoring system is of value in predicting left ventricular function in patients with acute infarction. With practice, the QRS score may be obtained in less than 1 minute. Therefore, this simple, inexpensive, and routinely available test is useful under these circumstances. However, caution should be applied in using the QRS scoring system in patients with old infarction. Although the QRS scoring system does not provide absolute measurements of the ejection fraction, it may help classify the patients into groups with normal or near-normal left ventricular function and mild to moderate left ventricular dysfunction. Furthermore, the size of infarction as assessed by thallium-201 correlated with left ventricular function in patients with acute or chronic infarction as well as in patients aft.er revascularization surgery. Finally, we should not be misled by a good p value, but should look rather at the spread of the data points. The ultimate purpose of these methods is to apply them clinically. It is clear that in individual patients, we cannot reliably predict left ventricular ejection fraction. The closest thing we can probably do is categorize the patients into those with low, moderate, and normal ejection fraction. This categorization could be done by using the QRS scoring system in acute infarction and by thallium imaging in patients with acute or chronic infarction. Acknowledgment: We thank Angelo Amenta for technical assistance, Wanda Klein for preparing the manuscript, and Edith Schwager for editorial assistance. Our special thanks
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to the anonymous reviewers who provided us with excellent reviews. Their comments and suggestions proved very useful and were incorporated in the manuscript.
References 1. Cohn PF, GorlinR, Cohn LH, Collins JS Jr. Left ventricular ejection fraction as a prognostic guide in surgical treatment of coronary and valvular heart disease. Am J Cardiol 1974;34:136-141. 2. Nelson GR, Cohn PF, Gorifn R. Prognosis in medically treated coronary artery disease: the value of ejection fraction compared with other measurements Circulation 1975;52:408-412, 3. Feild BJ, Russell RO Jr, Dowiing JT, Rackley CE. Regional left ventricular performance in the year following myocardial infarction. Circulation 1972:46:679-689. 4. Scheiberf HR, Henning H, Ashburn WL, Verba JW, Karliner JS, D’Rourke RA. Serial measurements of left ventricular ejection fraction by radionuclide angiography early and late after myocardial infarction. Am J Cardiol 1976;38:407-415. 5. Rigo P, Murray M, Strauss HW, Taylor D, Kelly D, Weisfeldt M, Pitt B. Left ventricular function in acute myocardial infarction evaluated by gated scintigraphy. Circulation 1974;50:678-684. 6. Battler A, Slutsky R, Karliner J, Froelicher V, Ashburn W, Ross J Jr. Left ventricular ejectibn fraction early after acute myocardial infarction: value for Dredictino mortalitv and morbiditv. Am J Cardiol 1980:45:197-202. 7. Wabken FJf, f&hoof JB, Sokole EB,ISamson G, Niffrik GJG, Lie KI, Durrer D, Wellens HJJ. Non-invasive visualtzation of acute myocardial infarction in man with thallium-201. Br Heart J 1975;37:741-744. a. Rude R, Parkey RW, Bonte FJ, Twleg D, Lewis S, Pulido J, Buja LM, Willerson JT. Clinical implications of the doughnut pattern of uptake in myocardial imaging with Tc-99m stannous pyrophosphate (abstr). Circulation 1977;56:Suppl lll:lll-46. 9. Schwartz KM, Turner JD, Sheffield T, Roitman DL, Kansal S, Papapietro SE, Mantle JA, Rackley CE? Russell RO Jr, Rogers WJ. Limited exercise y;;mg soon after myocardral infarction. Ann Intern Med 1981;94:72710. Starling M, Crawford MH, Kennedy GT, D’Rourke RA. Exercise testing early after myocardial infarction; predictive value for subsequent unstable angina and death. Am J Cardiol 1980;46:909-914. 11. Palmeri ST, Harrison DG, Cobb FR. A QRS scoring system for assessing left ventricular function after myocardial infarction. N Engl J Med 1982; 306:4-g.
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12. Selvester RH, Collier CR. Pearson RB. Analoa comouter model of the vectorcardiogram. Circulation 1965;31:45-53. ” ’ 13. Wagner OS, Freye CJ, Paimeri ST, Roark SF, Stack NC, Heker RE, Harreii FE, Seivester RH. Evaluation of a QRS scoring system for estimating myocardial infarct size. I. Specificity and observer agreement. Circulation 1982:65:342-347. 14. iskandrian AS, Hakki AH, Kane SA, Segai BL. Quantitative radionuclide angiography in assessment of hemodynamic changes during upright exercise: observations in normal subjects, patients with coronary artery disease and patients with aortic regurgitation. Am J Cardiol 1981;48:239246. 15. Rerych SK, Schoiz PM, Newman GE, Sabiston Jr DE, Jones RH. Cardiac function at rest and during exercise in normals and in patients with coronary heart disease: evaluation by radionuclide angiography. Ann Surg 1981; 187:449-463. 16. lskandrian AS, Segai BL. Thallium-PO1 myocardial scintigraphy: advantages and limitations. Arch Intern Med 1980:140:320-327. 17. Friedman TD, Greene AC, iskandrian AS, Hakki AH, Kane SA, Segal BL. Exercise thallium-201 myocardial scintigraphy in women: correlation with coronary arteriography. Am J Cardiol 1982;49:1632-1637, 16. iskandrian AS, Lichtenberg R, Segai BL, Mintz GS, Mundth ED, Hakki AH, Kimblris D, Bemis CE, Croll MN, Kane SA. Assessment of jeopardized myocardium in patients with one-vessel disease. Circulation 1982;65: 242-247. 19. iskandrian AS, Hakki AH, Segai BL, Kane SA, Amenta A. Assessment of the myocardial perfusion pattern in patients with multivessel coronary artery disease. Am Heart J (in press). 20. iskandrian AS. Seaai BL. Value of exercise thallium-201 imaaina in patients with diagnostk and nondiagnostic exercise electrocardiograms. Am J Cardiol 1981:48:233-238. 21. ldeker RE, Behar VS, Wagner GS, Starr JW, Starmer CF, Lee KL, Hackel DB. Evaluation of asynergy as an indicator of myocardial fibrosis. Crrcuiation 1978;57:715-724. 22. Bulkley BH, Silverman K, Weisfeldt ML, Burow R, Pond M, Becker LC. Pathologic basis of thallium-201 scintigraphic defects in patients with fatal myocardial injury. Circulation 1979;60:785-791. 23. Rouieau J, Griffith LSC, Strauss HW, Pitt B. Non-invasive assessment of segmental myocardial wall motion with thallium-201 perfusion scanning (abstr). Clin Res 1975;23:206A. 24. Bodenheimer MM, Banks VS, Hermann GA, Trout RG, Pasdar H, Heifant RH. Reversible asynergy: histopathologic and electrographic correlation in patients with coronary artery disease. Circulation 1976;53:792-796. 25. Sonnenblick EH, Strobeck JE. Derived indexes of ventricular and myocardial infarction. N Engl J Med 1977;296:978-982. 26. Buikiey BH, Hutchins GM, Bailey I, Strauss HW, Pitt B. Thallium-201 imaging and gated cardiac blood pool scans in patients with ischemic and idiopathic congestive cardiomyopathy. Circulation 1977;55:753-760.
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To determine the usefulness of the QRS scoring system in predicting left ventricular function, and the correlation between the QRS score, left ventricular ejection fraction, and the size of infarction, patients with acute or chronic infarction were studied by means of 12-lead electrocardiography, rest thallium-201 scintigraphy, and radionuclide angiography. In patients with acute infarction there was a statistically significant correlation between the QRS score and the left ventricular ejection fraction (n = 28, r = -0.81, p
with chronic infarction before they underwent coronary artery bypass, there was still a fair correlation between thallium score and left ventricular ejection fraction (n = 15, r = 0.61, p <0.02) but not between thallium score and QRS score (r = 0.03, p >0.05). In addition, in these patients with chronic infarction who underwent coronary revascularization, there was still a fair correlation between the postoperative thallium score and the postoperative left ventricular ejection fraction (r = 0.75, p
Left ventricular performance is an important factor in determining prognosis in patients with chronic coronary heart disease as well as after acute myocardial infarction.‘-” Techniques that have been used as prognostic indicators after acute infarction include evaluation of left ventricular ejection fraction and wall motion by radionuclide angiography’j and evaluation of the size of the scarred or ischemic myocardium by rest thallium-
201 scintigraphy.7 In addition, a specific appearance of the technetium-99m pyrophosphate images has been correlated with poor prognosis.8 Finally, exercise testing with or without thallium-201 imaging or radionuclide ventriculography has been used to categorize patients after acute infarction in different risk groups.9310 Recently, Palmeri et al,l’ using a QRS scoring system, were able to evaluate left ventricular function in patients with acute myocardial infarction. The QRS scoring system was still fairly accurate in predicting ventricular function up to 1 year after acute infarction in the group of patients they followed up. We were intrigued by the fact that a QRS score would work at all. If it does, then it is probably due to electrical
From the Likoff Cardiovascular Institute of Hahnemann Medical College and Hospital, Philadelphia, Pennsylvania. Manuscript received March 29, 1982; revised mariuscript received May 27, 1982, accepted June 16, 1982. Address for reprints: Abdulmassih S. Iskandrian, MD, Likoff Cardiovascular Institute, Hahnemann Medical College and Hospital, 280 North Broad Street, Philadelphia, Pennsylvania 19102.
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The size of the defect appears related to the left ventricular ejection fraction in both patients with acute infarction and those with chronic infarction. The QRS scoring system in patients with acute infarction and the size of the thallium defect in patients with acute or chronic infarction can categorize patients into those who have a low, moderate, and normal ejection fraction.
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forces from viable myocardium. The other noninvasive way to demonstrate viable myocardium is thallium-201 imaging. Furthermore, if there is a change in left ventricular ejection fraction as a result of improvement in myocardial flow by coronary artery bypass surgery, a change of QRS score might be expected as well and probably an improvement in the thallium perfusion defect. The purpose of this study was to compare the usefulness of the QRS scoring system of la-lead electrocardiograms with that of resting thallium-201 scintigrams in evaluating the left ventricular function of patients with acute or old myocardial infarction before and after coronary artery bypass.
TABLE I
ET AL
Criteria for Determining Point Score in the QRS Scoring System
Criteria (Number of Points) -
V4
0 130 ms (1) Q 240 ms (2) QZ30ms(l) Q 230 ms (1) Q 250 ms i3j Q 140 ms (2) Q 230 ms (1) Anv Q (1) R 250 &IS (2) R L40ms(l) AnyQorR120ms(l) R 260 ms (2) R 250 ms 111 Any Q or k’i30 Q 220 ms (1)
v5
Q 230 ms (1)
V6
Q 130
I, aVL aVF V,
v2
V3
Amplitude
Duration
Lead
Methods We studied 2 groups of’patients. The first group consisted of 37 patients with the diagnosis of acute infarction confirmed by typical history, electrocardiographic changes, and elevation in serum enzyme and specific cardiac isoenzyme levels. These patients were admitted to the coronary care unit over a 2month period. Thallium-201 images at rest are obtained in most patients with acute infarction admitted to our coronary care unit. The second group consisted of 43 patients with a documented history of myocardial infarction (more than 3 months before hospit,alization) as determined by history, electrocardiography, and cardiac enzyme levels. Sixteen of the 43 patients subsequently underwent coronary bypass because of angina pectoris. Standard 12-lead surface electrocardiograms were obtained with a 3-channel Hewlett-Packard recorder at a paper speed of 25 mm/s daily for 3 days and as clinically indicated afterward in 37 patients with acute myocardial infarction. If left ventricular hypertrophy, left anterior hemiblock (QRS axis Z-60”), right or left bundle branch block, ventricular preexcitation, or nonspecific intraventricular delay (QRS L 110 ms) was present on the electrocardiogram at 2 weeks, the patient was withdrawn from the study because the QRS score does not work in these patients. Using these exclusion criteria, we withdrew 8 patients from the study; therefore, 29 patients comprised the study group. Follow-up electrocardiograms were obtained at 2 weeks and compared with radionuclide angiograms performed at that time. Thallium-201 scintigraphy was performed at rest in 22 of the 29 patients 2 weeks after infarction as well. In the remaining 7 patients, thallium images were not obtained because either the pat,ient or the treating physician refused t,he studies. A transmural infarct was considered anterior or inferior when new Q waves 230 ms were present in the precordial leads or lead aVF, respectively. A non-Q-wave infarct was diagnosed when patients had a typical history of infarction with appropriate enzyme elevation, but in whom a Q wave 230 ms did not develop in the electrocardiogram. The QRS scoring system was based on the system developed by Selvester et al.l’.l:l Q- and R-wave durations and R/Q and R/S amplitudes and ratios in 10 of 12 standard electrocardiographic leads were analyzed (Table I). QRS scores could range from a minimal value of 0 to a theoretical maximum of 29 points. In patients with chronic infarction, radionuclide angiograms were not available soon after acute infarction. Each patient, however, subsequently underwent electrocardiography and radionuclide angiography. These patients were consecutive patients being evaluated in the nuclear cardiology laboratories for symptoms of angina pectoris. Sixteen of the 43 patients
FUNCTION-DePACE
Reproduced the American
ms (1)
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subsequently underwent coronary artery bypass surgery. In 15 of the 16 patients, thallium-201 images at rest were also available preoperatively. Ten to 14 days after surgery, electrocardiography, thallium-201 imaging at rest, and radionuelide angiography at rest were repeated in all but 1 of these 15 patients. Radionuclide angiography at rest was performed by means of a first-pass technique with a computerized multicrystal gamma camera (Baird-Atomic Systems-77) equipped with a l-inch (2.54 cm) parallel-hole collimator positioned anterior to the precordium. The study was inadequate in 1 patient because of a poor bolus injection. The technique for measuring the ejection fraction has been described in detail from thisI and other 1aboratories.l” In a previous study we showed an excellent correlation between radionuclide-derived ejection fractions and similar measurements obtained during cardiac catheterization.‘4 The technique for thallium imaging was previously described in reports from this laboratory. 1Rm~0 Quantitative analysis of the thallium images was performed by the perimetric method, as previously described from this laborat,ory.‘sl’” The size of the thallium-201 defect was determined by measuring the perimeter with a computerized Hewlett-Packard 982A digitizer and expressing it as a percentage of the total left ventricular perimeter in each projection (Fig. 1). The region of the valve was excluded. This method is similar t,o that used by Field et al:’ in assessing the extent of akinetic-dyskinetic segments by means of left ventriculography. The percentage of the average abnormal perimeter was determined from 3 projections. We also assessed the thallium scans by a scoring system. The image in each of the 3 projections was divided into 3 segments. Each segment was subjectively scored as follows: a score of 0 indicated minimal or no uptake; a score of 1 indicated severe reduction in uptake; a score of 2 indicated a moderate (but definite) reduction in uptake; a score of 3 indicated a mild (thus equivocal) reduction in uptake; and, finally, a score of 4 indicated normal uptake. Because the apex of the left ventricle usually has less thallium uptake than the remaining segments, presumably because the apex is thinner than the rest of the myocardium, we multiplied the score in
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QRS SCORE
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I
= 6
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the remaining segments by 2, yielding a score of 20 in each projection for a total score of 60 in 3 projections (Fig. 1). However, the results were not different even when a score of 4 was used for each segment. Therefore, a score of 40 would indicate that only two thirds of the left ventricle has normal uptake. Interpretations of the electrocardiogram, radionuclide angiograms, and thallium images were made independently without knowledge of the other results. The inter- and intraobserver variability in measuring the left ventricular ejection fraction was 2.2 f 1.5%i4 and the interobserver variability in measuring the thallium defects was 4 f 4%; the maximal difference was 14% in a patient with large defects whereas the intraobserver variability in measuring the thallium defects was 3 f 3%.18J9 The intraobserver variability in measuring the QRS score was 2 f 2% with a maximal difference of 5%. Statistical analysis was performed using Student’s t test or analysis of variance when appropriate. Values were expressed as the mean f standard deviation (SD) when indicated. A probability (p) value less than 0.05 was considered to represent a statistically significant difference. Correlation between the variables was assessed with linear regression analysis. Acute myocardial infarction: Of the 29 patients with acute infarction, the infarction was transmural (Q-wave infarction) in 20 patients: anterior in 9, inferior in 6, and both anterior and inferior in 5. The remaining 9 patients had non-Q-wave infarctions (nontransmural or subendocardial). There were 23 men and 6 women with an age range of 36 to 86 years (mean 61.2).
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FIGURE 1. The QRS score, left ventricular (LV) radionuclide angiogram, and the thallium-20’ images from a patient with acute anterior infarction. EF = ejection fraction; LAO = left anterior oblique projection.
QRS scoring: Seven of the 29 patients (24%) had a QRS score of 2 or less. All 7 patients had non-Q-wave infarctions. In the remaining patients the QRS score varied between 3 and 18. Patients with transmural infarctions had higher scores than patients with non-Q-wave infarctions (8.3 f 3.8 versus 1.6 f 1.2, p
ejection fraction and QRS score in the 28 patients with acute infarction in whom both studies were available (r = -0.61, y
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65 60 \
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FIGURE 2. Comparison between thallium score and thallium percentage (abnormal perimeter) in 22 patients with acute myocardial infarction (Ml). Ant = anterior; inf = inferior.
I;[
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Score
FIGURE4. Comparison between the thallium score and left ventricular ejection fraction (LV-EF) in 21 patients with acute myocardial infarction. Abbreviations as in Figure 2.
FIGURE3. Comparison between QRS score and left ventricular ejection fraction (LV-EF) in 28 patients with acute infarction. Abbreviations as in Figure 2.
(Fig. 4). Patients with small defects had higher ejection fractions than patients with larger defects. All 6 patients with a thallium score 140 had an ejection fraction 125%, whereas only 2 of 15 patients (13%) with a thallium score >40% had an ejection fraction <25% (p
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18
.
FUNCTION
DePACE ET At
.
16
n r
2h35 0.42x
25.3 DXO.001
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FIGURE 5. Comparison between QRS score and thallium score in 22 patients with acute myocardial infarction. Abbreviations as in Figure 2.
surgery consisted of 14 men and 2 women, aged 41 to 69 years. Eight of the 16 patients had transmural inferior infarctions, 3 had transmural anterior infarctions, 1 had both anterior and inferior infarction, 2 had non-Q-wave infarction, and 2 had bundle branch block. The ejection fraction measured in 15 patients increased from 34 f 8% preoperatively to 38 f 12% postoperatively (0.05
0
2
4
6
8
IO
12
14
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QRS Score FIGURE 6. Comparison between QRS score and left ventricular ejection fraction (LV-EF) in 41 patients with chronic myocardial infarction. Abbreviations as in Figure 2.
was observed in the correlation between the ejection fraction and the QRS score in patients with chronic myocardial infarction, the correlation was marginal (r = -0.51). More important, careful analysis of Figures 3 and 6 shows that for any given score the ejection fraction varied widely in patients with chronic infarction but not in patients with acute infarction. These results are similar in some respects to those of Palmeri et al” but also show some differences. First, these investigators followed the same cohort of patients with acute infarction over 2 years. However, we studied entirely different groups of patients, 1 with acute infarction and 1 with
Discussion The results of this study show that in patients with acute infarction, the QRS scoring system of Wagner et all” is reliable in predicting left ventricular function. Our study, therefore, confirms the conclusion of Palmeri et al,” although our correlation was lower than that reported by these investigators (r = -0.61 versus -0.88). It is worth emphasizing that the QRS scoring system cannot be used in patients with conduction defects, but can be used whether the myocardial infarction is transmural or nontransmural (non-Q-wave infarction). Although we studied a small group of patients with acute infarction, nevertheless these patients had a wide range of left ventricular function, QRS scores, and thallium scores and therefore these observations are likely to represent findings occurring more generally in other patients with acute infarction. Although a trend
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I
I
25
30
35
40
Thallium
I
45
50
55
60
Score
FIGURE 7. Comparison between thallium score and left ventricular ejection fraction (LV-EF) before and after coronary artery bypass surgery. Postop. = postoperative; preop. = preoperative.
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chronic infarction. This difference in method is related to the design of the study-prospective in the case of Palmeri et all’ and retrospective in our study. Second, even in the study of Palmeri et al,ll the correlation between the QRS score and the ejection fraction was lower at 1 year than the correlation 2 weeks after acute infarction. The exact reasons for the poorer correlation in patients with chronic infarction in both studies are not exactly known, but certain mechanisms can be postulated: for example, the disappearance of Q waves, a compensatory increase in the end-diastolic volume, and the effects of medications that may alter preload, afterload, and contractility. Finally, the presence or absence of myocardial &hernia at rest cannot be discounted. It appears that the common denominator between the QRS score and the left ventricular ejection fraction is the amount of infarcted myocardium. A significant correlation between the extent of myocardial fibrosis and left ventricular function has been shown.“l The extent of thallium defect has been shown to correlate with pathologically determined infarct size and with the contrast angiographic extent of asynergy.2”,“:J We studied the extent of the infarcted myocardium in patients with acute infarction by means of thallium-201 scintigraphy at rest, and in fact found a fair correlation between the size of the perfusion defect, the ejection fraction, and the QRS score (Fig. 3 and 4). We also found that in patients with chronic infarction, the correlation between the size of the defect and the ejection fraction was still fair, but again we found a poor correlation between the QRS score and the size of the thallium defect in patients with chronic infarction. In addition to fibrosis, resting thallium defects may represent chronic ischemia (or hypoperfusion). These perfusion abnormalities may be responsible for the segmental left ventricular wall-motion abnormalities seen in patients with chronic coronary artery disease in the absence of infarction: they may also explain the reversibility of these wall-motion abnormalities with nitroglycerin.24 This assumption needs further study. In the subgroup of patients with chronic infarction who underwent revascularization, the postoperative correlation between the ejection fraction and the size of the thallium defect was still fair (Fig. 7). However, as in the preoperative study, the correlation between the QRS score and the thallium score, or between the QRS score and the ejection fraction was poor. These results suggest that factors inherent in the QRS scoring system may be responsible for the poor correlation between the ejection fraction and the QRS score in patients with chronic infarction. Our method for assessing the defect size seen on thallium scans is simple and may be performed in any laboratory. Moreover, the good correlation between a thallium scoring system and the perimetric method used in this study indicates that the scoring system may be preferred because of its simplicity. As noted earlier, the correlation between the 2 methods is not unexpected
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ET AL
because both sets of data were derived from the same images. The ultimate validation of either method has to be made by a comparison with postmortem infarct size and probably with the contrast angiographic extent of asynergy as determined by other investigators.22,23 However, neither postmortem nor contrast angiographic data were available in our patients. Even the defect size in the thallium scans did not correlate perfectly with the left, ventricular ejection fraction (r = 0.70). There may be several related factors. First, some defects seen in the resting scans may represent ischemia (hypoperfusion) rather than scarring. Although it is our practice to obtain 4-hour delayed images after the initial resting images, the size of the defect as reported in this study represents the total defect size of both infarcted and possibly ischemic myocardium. Second, the left ventricular ejection fraction may have been affected by factors that modify the preload, afterload, and contractility.“” Third, as demonstrated in 2 patients with a small thallium defect in this study, the ejection fraction was disproportionately low compared with the size of the defect. In these patients an independent cardiomyopathic process may have been responsible for lowering the ejection fraction. It is well known that patients with nonischemic cardiomyopathy may have very low ejection fractions despite the presence of normal or near-normal left ventricular function26 (Fig. 4 and 7). Clinical implications: This study confirms a previous report that the QRS scoring system is of value in predicting left ventricular function in patients with acute infarction. With practice, the QRS score may be obtained in less than 1 minute. Therefore, this simple, inexpensive, and routinely available test is useful under these circumstances. However, caution should be applied in using the QRS scoring system in patients with old infarction. Although the QRS scoring system does not provide absolute measurements of the ejection fraction, it may help classify the patients into groups with normal or near-normal left ventricular function and mild to moderate left ventricular dysfunction. Furthermore, the size of infarction as assessed by thallium-201 correlated with left ventricular function in patients with acute or chronic infarction as well as in patients aft.er revascularization surgery. Finally, we should not be misled by a good p value, but should look rather at the spread of the data points. The ultimate purpose of these methods is to apply them clinically. It is clear that in individual patients, we cannot reliably predict left ventricular ejection fraction. The closest thing we can probably do is categorize the patients into those with low, moderate, and normal ejection fraction. This categorization could be done by using the QRS scoring system in acute infarction and by thallium imaging in patients with acute or chronic infarction. Acknowledgment: We thank Angelo Amenta for technical assistance, Wanda Klein for preparing the manuscript, and Edith Schwager for editorial assistance. Our special thanks
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to the anonymous reviewers who provided us with excellent reviews. Their comments and suggestions proved very useful and were incorporated in the manuscript.
References 1. Cohn PF, GorlinR, Cohn LH, Collins JS Jr. Left ventricular ejection fraction as a prognostic guide in surgical treatment of coronary and valvular heart disease. Am J Cardiol 1974;34:136-141. 2. Nelson GR, Cohn PF, Gorifn R. Prognosis in medically treated coronary artery disease: the value of ejection fraction compared with other measurements Circulation 1975;52:408-412, 3. Feild BJ, Russell RO Jr, Dowiing JT, Rackley CE. Regional left ventricular performance in the year following myocardial infarction. Circulation 1972:46:679-689. 4. Scheiberf HR, Henning H, Ashburn WL, Verba JW, Karliner JS, D’Rourke RA. Serial measurements of left ventricular ejection fraction by radionuclide angiography early and late after myocardial infarction. Am J Cardiol 1976;38:407-415. 5. Rigo P, Murray M, Strauss HW, Taylor D, Kelly D, Weisfeldt M, Pitt B. Left ventricular function in acute myocardial infarction evaluated by gated scintigraphy. Circulation 1974;50:678-684. 6. Battler A, Slutsky R, Karliner J, Froelicher V, Ashburn W, Ross J Jr. Left ventricular ejectibn fraction early after acute myocardial infarction: value for Dredictino mortalitv and morbiditv. Am J Cardiol 1980:45:197-202. 7. Wabken FJf, f&hoof JB, Sokole EB,ISamson G, Niffrik GJG, Lie KI, Durrer D, Wellens HJJ. Non-invasive visualtzation of acute myocardial infarction in man with thallium-201. Br Heart J 1975;37:741-744. a. Rude R, Parkey RW, Bonte FJ, Twleg D, Lewis S, Pulido J, Buja LM, Willerson JT. Clinical implications of the doughnut pattern of uptake in myocardial imaging with Tc-99m stannous pyrophosphate (abstr). Circulation 1977;56:Suppl lll:lll-46. 9. Schwartz KM, Turner JD, Sheffield T, Roitman DL, Kansal S, Papapietro SE, Mantle JA, Rackley CE? Russell RO Jr, Rogers WJ. Limited exercise y;;mg soon after myocardral infarction. Ann Intern Med 1981;94:72710. Starling M, Crawford MH, Kennedy GT, D’Rourke RA. Exercise testing early after myocardial infarction; predictive value for subsequent unstable angina and death. Am J Cardiol 1980;46:909-914. 11. Palmeri ST, Harrison DG, Cobb FR. A QRS scoring system for assessing left ventricular function after myocardial infarction. N Engl J Med 1982; 306:4-g.
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12. Selvester RH, Collier CR. Pearson RB. Analoa comouter model of the vectorcardiogram. Circulation 1965;31:45-53. ” ’ 13. Wagner OS, Freye CJ, Paimeri ST, Roark SF, Stack NC, Heker RE, Harreii FE, Seivester RH. Evaluation of a QRS scoring system for estimating myocardial infarct size. I. Specificity and observer agreement. Circulation 1982:65:342-347. 14. iskandrian AS, Hakki AH, Kane SA, Segai BL. Quantitative radionuclide angiography in assessment of hemodynamic changes during upright exercise: observations in normal subjects, patients with coronary artery disease and patients with aortic regurgitation. Am J Cardiol 1981;48:239246. 15. Rerych SK, Schoiz PM, Newman GE, Sabiston Jr DE, Jones RH. Cardiac function at rest and during exercise in normals and in patients with coronary heart disease: evaluation by radionuclide angiography. Ann Surg 1981; 187:449-463. 16. lskandrian AS, Segai BL. Thallium-PO1 myocardial scintigraphy: advantages and limitations. Arch Intern Med 1980:140:320-327. 17. Friedman TD, Greene AC, iskandrian AS, Hakki AH, Kane SA, Segal BL. Exercise thallium-201 myocardial scintigraphy in women: correlation with coronary arteriography. Am J Cardiol 1982;49:1632-1637, 16. iskandrian AS, Lichtenberg R, Segai BL, Mintz GS, Mundth ED, Hakki AH, Kimblris D, Bemis CE, Croll MN, Kane SA. Assessment of jeopardized myocardium in patients with one-vessel disease. Circulation 1982;65: 242-247. 19. iskandrian AS, Hakki AH, Segai BL, Kane SA, Amenta A. Assessment of the myocardial perfusion pattern in patients with multivessel coronary artery disease. Am Heart J (in press). 20. iskandrian AS. Seaai BL. Value of exercise thallium-201 imaaina in patients with diagnostk and nondiagnostic exercise electrocardiograms. Am J Cardiol 1981:48:233-238. 21. ldeker RE, Behar VS, Wagner GS, Starr JW, Starmer CF, Lee KL, Hackel DB. Evaluation of asynergy as an indicator of myocardial fibrosis. Crrcuiation 1978;57:715-724. 22. Bulkley BH, Silverman K, Weisfeldt ML, Burow R, Pond M, Becker LC. Pathologic basis of thallium-201 scintigraphic defects in patients with fatal myocardial injury. Circulation 1979;60:785-791. 23. Rouieau J, Griffith LSC, Strauss HW, Pitt B. Non-invasive assessment of segmental myocardial wall motion with thallium-201 perfusion scanning (abstr). Clin Res 1975;23:206A. 24. Bodenheimer MM, Banks VS, Hermann GA, Trout RG, Pasdar H, Heifant RH. Reversible asynergy: histopathologic and electrographic correlation in patients with coronary artery disease. Circulation 1976;53:792-796. 25. Sonnenblick EH, Strobeck JE. Derived indexes of ventricular and myocardial infarction. N Engl J Med 1977;296:978-982. 26. Buikiey BH, Hutchins GM, Bailey I, Strauss HW, Pitt B. Thallium-201 imaging and gated cardiac blood pool scans in patients with ischemic and idiopathic congestive cardiomyopathy. Circulation 1977;55:753-760.
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