Single Dose Exercise and Redistribution 201Thallium Scanning in the Diagnosis of Myocardial Ischemia and Coronary Artery Disease

Single Dose Exercise and Redistribution 201Thailium Scanning in the Diagnosis of Myocardial Ischemia and Coronary Artery Disease* Comparison with Exercise and Rest Electrocardiography, Coronary Arteriography and Left Ventriculography Harvey S. Hecht, M.D.; David E. Blumfield, M.D.;

James M. Hopkins, B.S.; Stuart G. Mirell, Ph.D.; and Maylene Wong, M.D.

To evaluate the accuracy of single dose tbaDium scanning (SDTS) utilizing exercise and four-hour redistribution images, 106 patients were evaluated; 91 had a >50 percent stenosis of at least one major vessel, 15 had no significant disease. Ischemia: compared to simultaneous ECG exercise tolerance test, SOTS was 86 percent vs 48 percent sensitive (P < 0.01), 100 percent vs 80 percent specific and 100 percent vs 94 percent predictive. Infarction: 79 percent of patients with ;>SO percent stenoses had persistently decreased perfusion on redistribution scanning compared to 43 percent with ECG Q waves (P < 0.01). Abnormally contracting segments: persistently decreased perfusion on redistribution scanning was 73 percent sensitive in the identification of abnormally contracting segments on

Conventional

thallium exercise and rest myo-

201

cardial imaging has been shown by numerous . investigators to be superior to stress electrocardiography in the diagnosis of myocardial ischemia and coronary artery disease.r" The use of separate rest and exercise injections, however, necessitates additional radiation, expense, delay and patient inconvenience. Recent work9-13 suggested that serial scanning within six hours of the exercise imaging utilizing a single dose of the isotope may be equally reliable. Blood et al 14 demonstrated that single and double dose scanning were similar to each other in 79 percent of patients and that both were superior to electrocardiography. In this study we extend the °From the Cardiology Section, Department of Medicine and the Department of Nuclear Medicine, Veterans Administration Wadsworth Medical Center and the University of California. Los Angeles. Supported by the Medical Research Service of the Veterans Adniinistration. Manuscript received April 9; revision accepted July 12. Reprint requests: Dr. Hecht, Wadsworth VA Hospital, Los Angeles 90073

left ventriculography compared to 33 percent by ECG < 0.01). Coronary artery disease: compared to exercise tolennce test and BeG Q waves, exercise and redistribution tbaDium scanniDg was 91 percent vs 71 percent sensitive (P < 0.01), 87 percent vs 73 percent specific and 98 percent VI 94 percent predictive in the detection of coronary artery disease. In conclusion, SDTS Is signUlcantly more sensitive than standard exercise tolerance testing and ECG panmeters in the diagnosis of Ischemia and the detection of patients with coronary artery disease and abnormally contracting segments and often an alternative to conventional double-dose exercise aDd rest 201tbaDium scanning.

Q waves (P

comparison of single dose exercise and redistribution 201thallium scanning with electrocardiography to a larger series of patients and provide a more detailed coronary angiographic and ventriculographic analysis. METHODS

One hundred six patients undergoing diagnostic cardiac catheterization for evaluation of suspected ischemic heart disease were studied with 201thallium within the week prior to or following catheterization. Patients were selected only on the basis of availability of the isotope. There were 104 men and two women, mean age 53 (range 31-71). All patients gave informed consent. Myocardial Imaging

Studies were performed with a stationary Searle PhoGamma IV and a portable Ohio Nuclear series 120 scintillation camera equipped with general all purpose collimators, ten minutes after injection of 1.5 mCi 201thallium ( New England Nuclear Corporation) during exercise.

CHEST, 77: 3, MARCH, 1980 SCANNING IN DIAGNOSIS OF MYOCARDIAL ISCHEMIA AND CORONARY ARTERY DISEASE •

myocardial regions and to the coronary vessels perfusing these regions according to the method of Hamilton et al. 2 The exercise and redistribution scans were independently evaluated by two trained observers without knowledge of clinical, angiographic or electrocardiographic data. Seventyfive percent of the scan interpretations were in total agreement and 25 percent represented a consensus after additional review of the scans.

Table l--CUnical Dam History Stable angina Unstable angina Atypical chest pain Asymptomatic Prior myocardial infarction Rest electrocardiogram Normal Significant Q waves ST and T abnormalities T wave abnormalities

69 4 28 5

50

Stress Testing and Electrocardiography

49 40 13 4

The spectrometer window was centered at 71 KeV with a 20 percent width. A lead shield 14 em in diameter was centered over the heart and 150,000 counts (equal to approximately 300,000 counts unshielded) were acquired in anteroposterior, 45° left anterior oblique, left lateral and 30 0 right anterior oblique positions. The camera head was rotated with the patient supine to enable exact repositioning for the redistribution study. The patient returned four hours after the isotope injection for redistribution scanning in the identical positions. Acquisition times per view ranged from four to ten minutes for the exercise study and slightly longer for the redistribution views. Data from the stationary scintillation camera were routed to a Medical Data Systems Bicam computer where the images were stored in a 128 x 128 matrix. A Medical Data Systems remote acquisition camera was used in conjunction with the portable scintillation camera and the data were transferred to the Bicam computer for analysis. A 64 X 64 submatrix encompassing the heart was extracted from the 128 X 128 matrix to eliminate extraneous surrounding structures. A uniform 25 percent count subtraction was applied to the 64 X 64 matrix based upon the highest value in that array and Polaroid photographs were taken. Defects in the redistribution study were defined as discrete areas of absent or clearly diminished activity and were considered to represent persistently decreased perfusion or "infarction" (see Discussion). Exercise-induced defects, reflecting reversible ischemia, were defined as discrete decreases in activity compared to the redistribution study. Defects were localized to

Stress testing was performed in the fasting state utilizing the maximal graded treadmill Bruce protocol-" with continuous electrocardiographic monitoring of simultaneous modified leads, aVF and V5 for the duration of the exercise and five minutes thereafter. Blood pressure was determined during each stage and during the post exercise period. 201Thallium was injected intravenously and Hushed through a 21 gauge heparin lock at the time when, because of chest pain, shortness of breath, generalized or leg fatigue, the patient felt he was unable to continue exercise for more than one additional minute. The test was terminated after the additional minute, and after five minutes of further monitoring, the patient was transported to the imaging room. The test was interpreted as positive if 1 rom of Hat or downsloping ST segment depression 0.08 second in duration occurred during or after exercise or if 2 mm upsloping depression was noted 0.08 second after the J-point. 16 Tests failing to meet these criteria were interpreted as negative irrespective of maximal heart rate achieved, Electrocardiographic evidence of infarction was based on pathologic Q waves in the resting ECG according to the criteria of the American Heart Association.t" True posterior myocardial infarction was evaluated according to the criteria of PerloH.1s

Coronary Arteriography and Left Ventriculography Selective coronary arteriography was performed by the Judkins technique. Injections of 8-10 ml of contrast medium (Renografin 76) were made in multiple oblique projections. Left ventriculography was performed in the 30 0 right anterior oblique position utilizing 7 ml/kg of Renografin 76. The angiograms were recorded on 35 rom film at 30 frames/

Table 2--Compari.on of Sira«le-Do.e Eserci.e and Redi.'ribution 201ThaUium Scannin«lf7i,h Eserci.e and R~, Elee'roeardio.,.aphy in ,he Dia.,..o.i. of Coronary Ar'ery Di.elUe Normal (n=15)

CAD (n=91)

Single Vessel (n=18)

Double Vessel (n=33)

Triple Vessel (n=40)

o (0%)

3 (20%) NS

78 (86%) 44 (48%) <0.01

15 (83%) 5 (28%) <.0.01

26 (79%) 15 (45%) <0.05

37 (93%) 24 (60%) <0.05

"Infarction" or persistently decreased perfusion Redistribution thallium scan Rest ECG P value

2 (13%) 1 (7%) NS

72 <79%) 39 (43%) <0.01

9 (50%) 2 (11%) <0.05

28 (85%) 16 (48%) <0.05

35 (88%) 21 (53%) <0.05

Ischemia and/or "infarction" or persistently decreased perfusion Exercise and redistribution thallium scan Exercise and rest ECG P value

2 (13%) 4 (27%) NS

88 (97%) 65 (71%) <0.01

16 (89%) 7 (39%) <0.01

33 (100%) 24 (73%) <0.05

39 (98%) 34 (85%) NS

Ischemia Exercise thallium scan Exercise ECG P value

Abbreviations: CAD = coronary artery disease-

380 HECHT ET AL

NS=not significant

CHEST, 77: 3, MARCH, 1980

Table 3-Seruitit1ity, Speci/ieitT and Predietil18 .t4eeu,..,. of Si.le Doae Tludlium SeGRfli~ Eleetroeardiop"aplaT in the Diapao.u of Coronary .t4mry DueaB

Thallium TP FN TN FP

Sensitivity

78

13 15 0

TP

86%

Ischemia

and

Coronary Artery Disease Ischemia + lor "Infarction" Thallium ECG

ECG 44 47

65 26 11

88 3

12

13 2

3

48% P
4

97%

71% P
TP+FN TN TN+FP

100%

80%

NS

87%

73%

NS

Predictive TP Accuracy TP+FP

100%

94%

NS

98%

94%

NS

Specificity

Abbreviations: FN = false negative: FP=false positive; NS=not significant; TN ==true negative; TP=true positive second. Two patients did not undergo left ventriculography. Stenoses of the main left, left anterior descending, left circumflex and right coronary arteries and the corresponding proximal normal segment were measured with calipers to the nearest 0.5 mm by an independent observer and the greatest diameter reduction in any projection was recorded. Stenosis equal to or "greater than 50 percent diameter reduction was considered to represent significant disease. End-diastolic and end-systolic frames of the left ventriculogram were traced, superimposed and divided into five segments according to the criteria of the American Heart Association: 17 anterobasal, anterolateral, apical, diaphragmatic and posterobasal. Two independent observers, working without knowledge of the coronary arteriographic electrocardiographic and imaging data, qualitatively evaluated the motion of each segment as normal, hypokinetic or akinetic/ dyskinetic. Ninety-one percent of the segmental evaluations were in exact agreement and a consensus was reached on the remaining segments after additional review. The arterial supply to each segment was determined by observing the distribution of the major vessels in the 30° right anterior oblique projection. Specific attention was paid to individual variations, eg,left anterior descending artery coursing around the apex to supply part of the inferior wall. In general, the left circumflex distribution could not be included in the segmental analysis since left anterior oblique angiograms were not performed. Fourteen patients had a dominant left circumflex and were included in the analysis. Finally, perfusion defects on the thallium image and abnormally contracting segments on ventriculography in the distribution of the left anterior descending, right coronary and dominant left circumflex arteries were correlated with each other. Results were analyzed by Student's t test and McNemar's test. 1 9 REsULTS

The clinical data are shown in Table 1. Ischemia (Ta,bles 2 and 3 ) Sensitivity:" Of 91 patients with significant coronary stenoses, single dose thallium scanning was positive for ischemia in 78 (86 percent) compared to 44 (48 percent) for exercise ECG (P < 0.01); 15 of 18 (83 percent) vs 5 of 18 (28 percent) for single vessel disease (P < 0.05), 26 of 33 (79 percent) vs

15 of 33 (45 percent) for double vessel disease (P < 0.01) and 37 of 40 (93 percent) vs 24 of 40 (60 percent) for triple vessel disease (P < 0.01). Single dose thallium scanning was positive in 32 of 39 (82 percent) with Q wave evidence of myocardial infarction compared to 19 of 39 (49 percent) by exercise ECG (P < 0.01). In 52 patients without Q wave evidence of myocardial infarction, single dose thallium scanning was positive in 46 (88 percent) compared to 25 (49 percent) by exercise ECG (P < 0.01). Specifleity't " and Predictive Accuracy:t None of the 15 patients without significant stenoses had positive single dose thallium scanning for ischemia compared to 3 positive exercise ECG responses. Thus, the specificity was 100 percent for single dose thallium scanning compared to 80 percent for exercise ECG (P == NS). The predictive accuracy of single dose thallium scanning was 100percent vs 96 percent by exercise ECG (P == NS) Exercise-induced Chest Pain (Table 4)

Fifty-eight patients (64 percent) with significant stenoses and 6 (40 percent) with normal vessels experienced their characteristic chest pain during the treadmill exercise. Utilizing this response as a sign of ischemia yields a higher sensitivity than for exercise ECG alone (64 percent vs 48 percent, p = NS), but still significantly lower (P < 0.05) than for single dose thallium scanning. When combined with exercise ECG (70 of 91, 77 percent) there is • sensitivity: true positives true positives + false negatives o·specmcity: true negatives true negatives false positives tpredictive accuracy: _tru_e~p_os_iti_·v_e_s _ true positives false positives

+

+

CHEST, 77: 3, MARCH, 1980 SCANNING IN DIAGNOSIS OF MYOCARIIIL ISCHEMIA lID COROllARY ARTERY DISEASE 311

Table 4--CompariMln of Siqle D.e Eserci.e and Redi.,ribution 201Tlaallium Scanning ",i,h Esercue Chea, Pain and Eserciae and Rut Eleelrocardi".raph,. in ,lae DiapMia of Coronary Artery Dueae

Ischemia Exercise chest pain Exercise thalli um scan Exercise chest pain and/or ECG Ischemia and/or MI Exercise and redistribution thallium scan Exercise chest pain and/or exercise and rest ECG

Normal (n == 15)

CAD (n==91)

6 (40%) o (0%) 8 (53%)

58 (64%) 78 (86%) 70 (77%)

64%~ 86% 77%

P<.OI P==NS

2 (13%)

88 (97%)

97%1

8 (53%)

79 (87%)

87%

P==NS

Sensitivity

Specificity

6O%~

P<.05 P<.05

100% 47%

87%1 47%

P<.05

Predictive Accuracy

91%t

100% 90%

98%1 91%

P==NS P==NS

P==NS

Abbreviations: CAD == coronary artery disease; MI == myocardial infarction; NS == not significant

no significant difference from single dose thallium scanning. However, there is a concomitant significant reduction in specificity: 60 percent vs 100 percent for exercise chest pain vs single dose thallium scanning (P < 0.05) and 47 percent for exercise chest pain and/or exercise ECG vs single dose thallium scanning (P < 0.05).

Persistently Decreased Perfusion or "Infarction" and Abnormally Contracting Segments

Of the 91 patients with significant stenoses, fourhour redistribution thallium scanning was positive for persistently decreased perfusion or "infarction" in 72 (79 percent) vs 39 (43 percent) for rest ECG Q wave evidence of infarction (P <.. 0.01); 9 of 18 (58 percent) vs 2 of 18 (11 percent) for single vessel (P < 0.05), 28 of 33 (85 percent) vs 16 of 33 (48 percent) for double vessel (P < 0.05) and 35 of 40 (88 percent) vs 21 of 40 (53 percent) for triple vessel disease (P < 0.05) (Table 2). Persistently decreased perfusion was noted in the distribution of 116 vessels in the 89 patients with

significant disease who had left ventriculograms. One hundred and two were in the. distribution of the left anterior descending, right coronary or dominant left circumflex artery and corresponding abnormally contracting segments in the distribution of these vessels in the 30° right anterior oblique ventriculogram were found in 87 (85 percent); 53 were hypokinetic and 34 were akinetic/ dyskinetic. Thirty-nine of these were accompanied by ECG evidence of transmural infarction; 17 were hypokinetic and 22 were akinetic/ dyskinetic. Of the 15 without corresponding abnormally contracting segments, 14 were in the distribution of vessels with stenoses averaging 90 percent and 4 of these had ECG evidence of transmural infarction. The remaining one was in the distribution of a normal vessel. In the absence of left anterior oblique ventriculograms, the 14 redistribution defects in the posterolateral left circumHex distribution could not be correlated with abnormally contracting segments. However, these areas were associated with left circumHex stenoses averaging 90 percent. Two patients without coronary disease had

Table S--Deteedon of .4bnonnaU,. Contraedn« Se.menh by 201 TlaaUium RedUlribudon Sctmniq and Re.. EKG

Thallium Redistribution Defect TP FN

TN

Hypo 55 33

Akin/Dysk 34 0

FP

ECGMI Hypo 18 70

Hypo + Akin/Dysk 89 33 72 15

Akin/Dysk 22 12

Hypo-l-Akin/Dysk 40

82 83 4

Thallium Redistribution 63% 100% 73%

ECGMI 20% 65% 33%

TN TN+FP

83%

95%

NS

Predictive TP Accuracy TP+FP

86%

91%

NS

TP Sensitivity TP+FN Specificity

Hypo Akin/Dysk Hypo + Akin/Dysk

P
Abbreviations: Akin/Dysk==akinesia/dyskinesia.; FN =-false negative; FP-false positive; Hypo-hypokinesia; NS==not significant; TN ==true negative; TP==true positive

382 HECHT ET AL

CHEST, 77: 3, MARCH, 1980

defects on redistribution scanning and one of these had infarction by ECG. Both had corresponding hypokinetic areas. Abnormally contracting segments were noted in the distribution of 122 vessels in the entire study group, 88 with hypokinesia and 34 with akinesia/ dyskinesia (Table 5). Corresponding thallium redistribution defects were present in 89 (73 percent) compared to 40 (33 percent) with corresponding ECG evidence of infarction. Compared to ECG evidence of infarction, thallium redistribution defects were 73 percent vs 33 percent sensitive for all abnormally contracting segments (P < 0.01), 63 percent vs 20 percent sensitive for hypokinesia (P < 0.01) and 100 percent vs 65 percent for akinesia/dyskinesia (P < 0.01). There were no significant differences in the specificity and predictive accuracy: 83 percent vs 95 percent specificity and 86 percent vs 91 percent predictive accuracy. Of the 73 patients with significant coronary disease and abnormally contracting segments, redistribution imaging identified 62 (85 percent) vs 36 (49 percent) by restECG (P < 0.01) . Coronary Artery Disease: Ischemia and/or "Infarction" (Tables2and3)

Sensitivity: Of the 91 patients with significant

stenoses, the combination of single dose exercise and redistribution scans identified 88 (97 percent) compared to 65 (71 percent) by exercise and rest ECG (P < 0.01) ; 16 of 18 (89 percent) vs 7 of 18 (39 percent) for single vessel disease (P < 0.01) , 33 of 33 (100 percent) vs 24 of 33 (73 percent) for double vessel disease (P < 0.05) and 39 of 40 (90 percent) vs 34 of 40 (85 percent) with triple vessel disease (P = NS). Only one patient was identified by ECG alone, with negative thallium scanning. If exerciseinduced chest pain is included with exercise and rest ECG, the sensitivity of stress testing is increased to 87percent (Table 4) . Specificity and Predictive Accuracy: Two of the 15 patients without significant stenoses had positive single dose thallium scanning for persistently decreased perfusion and four had positive exercise and/ or rest ECG. The specificity was 87 percent for thallium scanning compared to 73 percent for ECG (P = NS). The predictive accuracy was 98 percent for thallium scanning compared to 94 percent for ECG (P = NS ). If exercise-induced chest pain is included with exercise and rest ECG, the specificity is Significantly reduced: 47 percent vs 87 percent for exercise chest pain and exercise and rest ECG vs single dose thallium scanning. Exercise Response: Average percentage of pre-

"

AVF

AVF

FIGURE 1. On the left are the exercise ECG and exercise 201thillium scans demonstrating significant ST depression in all three leads and inferior, apical, posterolateral and anteroseptal ischemia. On the right are the pre-exercise ECG and the redistribution 201thallium scan which demonstrates no abnormalities. Coronary arteriography · revealed 100 percent left anterior descending, 95 percent left circumflex and 50 percent right coronary artery stenosis. Left venanteroposterior, LAO left anterior triculography demonstrated apical hypokinesia. AP oblique, LL = left lateral, REDIST = redistribution.

=

=

CHEST, 77: 3, MARCH, 1980 SCANNING IN DIAGNOSIS OF MYOCARDIAL ISCHEMIA AND CORONARY ARTERY DISEASE 383

FiCURE 2. The exercise ECG demonstrates no significant ST segment changes . 201Thallium scanning reveals apical and anteroseptal ischemia with exercise and apical and anterior infarction on the redistribution scan (in the left lateral view). Coronary arteriography revealed 85 percent left anterior descending and 75 percent left circumHex stenosis. Left ventriculography demonstrated anterolateral and apical dyskinesia and posterobasal and diaphragmatic anteroposterior, hypokinesia. The resting ECG was diagnostic of anteroseptal infarction. AP LAO = left anterior oblique, LL = left lateral, REDIST = redistribution.

=

dieted maximal heart rate achieved with exercise was 82 percent (SD = 15 percent) for positive single dose thallium scanning, 80 percent (SD = 15

percent) for positive exercise ECG, 73 percent (SD = 14 percent) for negative single dose thallium scanning and 82 percent (SD = 9 percent) for nega-

FiCURE 3. The exercise ECG demonstrates no signifioant ST segment changes. 201Thallium scanning reveals inferior, apical and anteroseptal ischemia with exercise and a normal redistribution scan. Coronary arteriography revealed a totally occluded left anterior descending with collaterals from the right coronary artery, coursing around the apex to supply part of the inferior wall. The left ventriculogram displayed apical and anterolateral hypokinesia. AP anteroposterior, LAO = left anterior oblique, LL = left lateral, REDIST = redistribution.

=

364 HECHT ET At

CHEST, 77: 3, MARCH, 1980

tive exercise ECG. There were no statistical differences between any of these values by Student's t test. Thirty-six patients experienced chest pain and had exercise-induced significant ST segment depression, 28 had chest pain alone and 11 had ST segment depression alone.

Examples of single dose thallium scanning in pa-

tients with significant stenoses are shown in Figures 1-3. DISCUSSION

The superiority of 201thallium exercise and rest imaging over exercise and rest ECG for the detection of ischemia and coronary artery disease has been established by many studies.!" Demonstration of early redistribution of thallium imaging9-13 suggested that serial scanning utilizing a single dose of 201thallium might oHer similar superiority and the report of Blood et al 14 confirmed this impression.

Ischemia In this study, the findings of significantly higher sensitivity of single dose thallium scanning in the detection of ischemia adds further support to this technique. The excellent results for single vessel disease are not surprising since exercise-induced perfusion deficits might be expected to be more striking when only a single area of myocardium is involved. Under these circumstances the contrast between involved and normal areas may be greater than in situations where there is less normally perfused myocardium .available for comparison as might occur with multiple vessel involvement. In support of the results in this study, Botvinick et al4 demonstrated no significant differences in sensitivities for single, double and triple vessel disease in contrast to Bailey et all who reported sensitivities of 43 percent for single vessel, 55 percent for double vessel.and 80 percent for triple vessel disease. The 86 percent sensitivity of single dose thallium scanning for all patients is similar to the 89 percent of Blood et al14 for single dose scanning and to the 85-95 percent for conventional double dose scannings 4.S•14 reported by several centers. It is higher than the 55-66 percent of other investigators.1.3.6 The use of computer processing and background subtraction is unlikely to have led to overinterpretation and therefore to the high sensitivities since there was no concomitant reduction in specificity. The slightly higher incidence of patients with triple vessel coronary disease is unlikely to be significant since there were no differences in sensitivities between patients with single, double or triple vessel disease. In addition, differences in the extent of the

stress testing is not a probable explanation since all studies reported symptom-limited, maximal stress testing. The 48 percent incidence of positive exercise ECG is lower than the 65-66 percent reported by some investigatorsv's and similar to the 38-52 percent reported by others,1.3.S Chaitman et al20 have

shown that exercise ECG sensitivity can be improved by the use of 11-14 leads compared to a single lead. The employment of such a system might have resulted in a higher sensitivity in this study, although both high and low sensitivities have been reported using either single 3.4 or multiplev'" lead systems. The low sensitivity in this study may be partially accounted for by the relatively low percentage of maximal predicted heart rates achieved. The use of propranolol in many patients may be responsible. However, it must be emphasized that exercise testing was maximal, limited only by symptoms which prevented continuation of exercise for more than one minute after injection of 201thallium. Particular care was paid to encouraging maximal performances. Moreover, there were no significant diHerences in percentage of predicted maximal heart rate between patients with positive or negative exercise ECG or thallium scan. . The 100 percent specificity in patients without significant coronary disease is similar to the 89-100 percent specificity reported in other series 1,3,4,6-8 employing two-dose' scanning and greater than the 69 percent of Blood et al 14 for the single-dose technique. The specificity and predictive accuracy in this study might have been lower in a larger population of patients without significant coronary disease. In the other studies, the percentage of normal patients was also relatively low and they are subject to the same problems concerning specificity and predictive accuracy that are introduced by a skewed population. The addition of exercise-induced chest pain as an index of ischemia significantly increased the sensitivity, but decreased the speciBcity of the exercise ECG to an unacceptable level. Bailey et all reported a similar increased sensitivity, comparable to that of thallium scanning, but had no reduction in their specificity of 100 percent by exercise ECG when chest pain was considered. However, 85 percent of their normal patients were volunteers without any history of chest pain compared to 100 percent with a history of chest pain in the normal patients in this study. Ritchie et ala reported a 66 percent incidence of exercise-induced chest pain in their patients with significant coronary disease (comparable to the 64 percent in this study) but reported a 12 percent incidence in their normal population referred for

CHEST, 77: 3, MARCH, 1980 SCANNING IN DIAGNOSIS OF MYOCARDIAL ISCHEMIA AND CORONARY AmRY DISEASE •

suspected coronary disease ( compared to 40 percent in this study). In view of the relatively small numbers of normal patients involved, the discrepancy may reflect sampling differences. It is of interest that Ellestad et al21 found exercise chest pain to be a poorly discriminating variable in the differentiation of true and false positive exercise tests. Persistently Decreased Perfusion or "Infarction" and Abnormally Contracting Segments

Single-dose thallium scanning demonstrated signiflcant superiority compared to rest ECG in the detection of "infarction" (79 percent vs 43 percent, P < 0.01). However, in the absence of post-mortem or operative evidence of infarction it is difficult to establish a standard against which the true incidence of infarction can be measured. Electrocardiography " often underestimates the incidence of infarction22 and, if used as the standard for infarction, would result in a large number of false positive diagnoses by thallium scanning if redistribution defects were considered to be equivalent to infarction. Abnormally contracting segments frequently occur in the presence of normal myocardium." often improve following nitroglycerin.P' post-extrasystolic potentiation 25 and coronary artery bypass surgery.i" and are therefore not acceptable as a standard for myocardial infarction. Several studies have shown good correlations between both two-hour redistribution" and rest 28 perfusion defects and areas of irreversible asynergy suggesting the presence of infarction in these areas, but histopathologic data were not available for confirmation. Blood et al 14 and Ritchie et al29 found that defect size on four hour redistribution scanning was larger than on rest scanning in 21 percent'! and 37 percent'" of patients undergoing both procedures, and conclusions concerning the extent of myocardial damage from redistribution scanning are, therefore, questionable. Further ambiguities have been introduced by recent evidence demonstrating: a) redistribution at 24 hours of defects on four-hour post-exercise scans in the distribution of severely stenotic vessels." and b) redistribution following rest injection in patients with stable angina." Thus, the diagnosis of infarction on either four-hour redistribution or rest scans is problematical and has undoubtedly been overdiagnosed in previous studies. "Persistently decreased perfusion" rather than "infarction" may be a more appropriate description, but the latter has been incorporated into the scanning nomenclature. "Infarction" is therefore used interchangeably with "persistently decreased perfusion" in this report, but the above qualifications must be kept in mind.

386 HECHT ET AL

In the present study, abnormally contracting segments were found in the distribution of 85 percent of vessels with corresponding redistribution 201thaI_ lium defects. Almost half (39/87) were accompanied by ECG evidence of transmural infarction and these presumably represent real myocardial damage. The 47 defects accompanied only by abnormally contracting segments (12 akinetic/ dyskinetic and 35 hypokinetic) without ECG evidence of infarction mayor may not represent true infarction. At the very least they represent more severe perfusion deficits than those that normalized at four hours. Their significance lies primarily in serving to identify areas affected by severe coronary artery disease. It is in this context that comparison with specific ECG evidence of coronary disease (ie, Q waves) is valid. The 14 redistribution defects without corresponding abnormally contracting segments that were in the distribution of stenoses averaging 90 percent might have normalized on scans performed at a later time. The single defect that was associated with a normal vessel may represent a false positive result. In the patients without coronary disease, the two instances of persistent defects on redistribution scanning were associated with corresponding hypokinesia without apparent etiology. Hypokinesia was also noted in the distribution of 16 percent of all the normal vessels in the study. The presence of persistently decreased perfusion on redistribution scanning was significantly more sensitive in the detection of patients with abnormally contracting segments (hypokinetic and akineticI dyskinetic) than" ECG evidence of infarction (83 percent vs 48 percent, P < 0.01) and is thus more useful in the evaluation of ventricular function in addition to providing Information concerning myocardial perfusion. Other investigators have reported the superiority of double dose 1•3•6 and single dose 14 thallium scanning to rest ECG in the detection of infarction, but in most of the series a detailed angiographic wall motion analysis was not performed. Moreover, the determination of sensitivity and specificity in those series is probably not valid in light of the difficulties discussed above in determining a standard for myocardial infarction. Coronary Artery Disease: Ischemia and/ or "lniarc-

tum"

Single dose thallium scanning was significantly more sensitive than the ECG in the diagnosis of coronary artery disease (97 percent vs 71 percent, P < 0.01) and equally specific and predictive. Analysis of sensitivity, specificity and predictive accuracy ap-

CHEST, 77: 3, MARCH, 1980

pears justified in this grouping since"infarction," or persistently decreased perfusion, is used in the context of a marker for coronary artery disease as discussed above rather than to define infarction per set The high sensitivity in this study is similar to the 93

percent of Blood

et

al14 for both the single and

double dose techniques and higher than the 75-77 percent for the double dose method reported by others.P As with ischemia, the inclusion of exerciseinduced chest pain as a marker for coronary artery disease (Table 4) increases the sensitivity of ECG stress testing to a level comparable to thallium scanning but results in an unacceptable reduction in specificity. Clinical Implications

This study provides additional evidence for the superiority of single dose thallium scanning over electrocardiography in the diagnosis of ischemia and "infarction" in a population with a high prevalence of coronary artery disease and, by virtue of the excellent results, suggests that this procedure is an excellent alternative to the conventional double dose exercise and rest technique. ACKNOWLEDGMENTS: We would like to thank Kaye Cherry for her secretarial assistance in preparation of the manuscript, Dr. Janet EIashoff for the statistical analyses and the Nuclear Medicine and Cardiac Catheterization Lab-. oratory personnel for technical assistance in performance of the studies. REFERENCES

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of TI-201 stress myocardial scintigraphy. J Nuc! Moo 18:509-516, 1977 6 Ritchie JL, Zaret BL, Strauss HW, et al: Myocardial imaging with thallium-201 at rest and exercise-a multicenter study: coronary angiographic and electrocardiographic correlations. ( abstr) J Nuc1 Moo 18: 642, 1977 7 Klein GJ, Kostuk WJ: Diagnostic accuracy of non-invasive stress myocardial perfusion imaging. (abstr) Circulation 53: Suppl II, 207, 1976

8 Trobaugh GB, Hamilton GW, Ritchie JL, et al: Usefulness and limitations of thallium-201 for detection of coronary artery disease based on Bayes Theorem (abstr)

Am J(JlrdioI411441~ 1876 9 Pohost GM, Zir LM, Moore RH, et a1: Differentiation of transiently ischemic from infarcted myocardium by serial

imaging after a single dose of thallium-201. Circulation

55:294-302, 1977 10 Beller GA, Pohost GM: Mechanism for thallium-201 redistribution after transient myocardial ischemia. (abstr) Circulation 55:Suppl III: 141, 1977 11 Beller GA, Pohost GM: Time course and mechanism of resolution of thallium-201 defects after transient myocardial ischemia. (abstr) Am J Cardiol 41:379, 1978 12 Schwartz JS, Ponto R, Carlyle P: Early redistribution of thallium-201 after temporary ischemia. Circulation 57: 332-335, 1978 13 Hor G, Sebening H, Sauer E, et al: Thallium-201 redistribution in coronary heart disease (CUD). Early and delayed myocardial scans. (abstr) J Nuel Med 18:599, 1977 14 Blood DK, McCarthy DM, Sciacca RR, et al: Comparison of single-dose and double-dose thallium-201 myocardial perfusion scintigraphy for the detection of coronary artery disease and prior'myocardial infarction. Circulation 58: 777-778, 1978 15 Bruce RA: Exercise testing of patients with coronary heart disease: principles and normal standards for evaluation. Ann Clin Res 3:323-332, 1971 16 Stuart RJ, Ellestad MH: Upsloping S-T segments in exercise stress testing. Six year follow-up study of 438 patients and correlation with 248 angiograms. Am J Cardiol 37: 19-21, 1976 17 A reporting system on patients evaluated for coronary artery disease. Report of the Ad Hoc Committee for grading of coronary artery disease, Council on Cardiovascular Surgery, American Heart Association. Circulation 51: ( Suppl IV) 7-40, 1975 18 Perloff JK: The recognition of strictly posterior myocardial infarction by conventional scalar electrocardiography. Circulation 30:706-718, 1964 19 Siegel S: Nonparametrie Statistics. New York, McGraw Hill, 1956, p 63 20 Chaitman BR, Bourassa MG, Wagniart P, et al: Improved efficiency of treadmill exercise testing using a multiple lead ECG system and basic hemodynamic exercise respouse. Circulation 57:71-79, 1978 . 21 Ellestad MH, Savitz S, Bergdall D, et al: The false positive stress test. Multivariate analysis of 215 subjects with hemodynamic, angiographic and clinical data. Am J Cardiol 40:681-685, 1977 22 Horan LG, Flowers NC, Johnson JC: Significance of the diagnostic Q wave of myocardial infarction. Circulation 43:428-436, 1971 23 Hutchins GM, Bulkley BH, RidolB RC, et al: Correlation of coronary arteriograms and left ventriculograms with postmortem studies. Circulation 56: 32-37, 1977 24 McAnulty JH, Hattenhauer MT, Rosch JR, et at: Improvement in left ventricular wall motion following nitroglycerin. Circulation 51: 140-145, 1975 25 Dyke SH, Cohn PF, Gorlin R, et al: Detection of residual myocardial function in coronary artery disease using post extrasystolic potentiation. Circulation 50: 694-699, 1974 26 Helfant RH, Pine R, Meister SG, et al: Nitroglycerin to unmask reversible asynergy. Correlation with post coronary bypass ventriculography. Circulation 50: 108-113,

CHEST, 77: 3, MARCH, 1980 SCANNING IN DIAGNOSIS OF MYOCARDIAL ISCHEMIA AND CORONARY ARTERY DISEASE 387

1974 27 Bodenheimer MM, Banka VS, Fooshee C, et al: Relationship between regional myocardial perfusion and the presence, severity and reversibility of asynergy in patients with coronary heart disease. Circulation 58:789-795, 1978 28 Massie BM, Botvinick EH, Brundage BH, et al: Relationship of regional myocardial perfusion to segmental wall motion. A physiologic basis for understanding the presence and reversibility of asynergy. Circulation 58: 11541163, 1978

29 Ritchie IL, Albro PC, Caldwell JH, et al: ThaIIium-201 myocardial imaging: a comparison of the redistribution and rest images. J Nucl Med 20:477-483, 1979 30 Berman D, Maddahi J, Charuzi Y, et aI: Rate of redistribution in T1-201 exercise myocardial scintigraphy: Inverse relationship to degree of coronary stenosis. (Abstr). Circulation 57: Suppl II, 63, 1978 31 Berger BC, Watson DW, Burwell LR, et al: Redistribution of thallium-201 at rest and effect of coronary bypass surgery. Circulation 57: Suppl II, 63, 1978

FIFTH INTERNATIONAL CONFERENCE ON LUNG SOUNDS The Fifth International Conference on Lung Sounds will be held in London, England, September 15-16, sponsored by the International Lung Sounds Association. Papers for presentation during the conference will be selected by the Program Committee. Abstracts should not exceed 200 words and should be submitted by May 1. Abstracts may relate to any aspect of lung sounds.

Abstracts, questions or requests for registration forms should be addressed to Raymond L. H. Murphy, Jr., M.D., 1153 Centre Street, Boston 02130.

368 HECHT ET AL

CHEST, 77: 3, MARCH, 1980