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Body surface distributions of ST segment changes after exercise in effort angina pectoris without myocardial infarction
Body surface distributions of ST segment changes after exercise in effort angina pectoris without myocardial infarction To investigate the sites of exercise-induced ST segment changes on the body surface in effort angina pectoris without myocardial infarction, we performed 87-lead ECG mapping in 61 patients before and 1.5 and 5 minutes after treadmill exercise. ST segment depression most often occurred in the left anterior chest leads and ST segment elevation developed mainly in the right upper chest leads. There was a good correlation between the number of lead points that showed ST segment depression (nSTd) and the number of those that showed ST segment elevation (nSTe) 1.5 minutes after exercise (r = 0.92). From 1.5 to 5 minutes after exercise, changes in nSTd for individual patients correlated weil with changes in nSTe (r = 0.89). It was suggested that the ST segment elevation observed in this study directly reflected the subendocardial ischemia of the left ventricle. In patients with one-vessel disease (n = 32), there was wide overlap in the sites of ST segment changes among patients with left anterior descending artery disease (n = 19) those with left circumflex artery disease (n = 6) and those with right coronary artery disease (n = 7). These findings should lead to a better understanding of exercise-induced ST segment changes for the diagnosis of coronary artery disease. (AM HEART J 110:949, 1985.)
Isao Kubota, M.D., Kozue Ikeda, M.D., Taketsugu Ohyama, M.D., Michiyasu Yamaki, M.D., Sukehiko Kawashima, M.D., Akira Igarashi, M.D., Kai Tsuiki, M.D., and Shoji Yasui, M.D. Yamugata, Japan
Ischemic ST segment changes (depression and elevation) are widely used indices for detection of myocardial ischemia in exercise testing.’ However, there are few data on body surface distribution patterns of ST segment changes2-5 because the number of lead points to detect such changes has been limited. These data are needed to clarify the clinical significance of ST segment changes in the diagnosis of coronary artery disease. The purpose of this study was to investigate the distribution patterns of exercise-induced ST segment changes on the body surface in effort angina pectoris without myocardial infarction by means of a body surface mapping technique. METHODS Study population. Of 506 consecutive patients who underwent treadmill exercise testing, using body surface mapping and coronary arteriography to assess coronary artery disease, 61 patients (45 men and 16 women)
satisfied all the following criteria and formed the study population: (1) The patients were between 41 and 72 (mean 58) years of age. (2) They were diagnosed as having stable effort angina pectoris. (3) They had no history of previous myocardial infarction established by typical chest pain, serum enzyme changes, and ECG findings. (4) They had no wall motion abnormalities such as akinesis or dyskinesis on left ventriculogram. (5) They had no intraventricular conduction disturbances or ST segment changes on resting 12-lead ECGs. (6) They had no clinical or ECG evidence of variant angina pectoris or spontaneous angina at rest. (7) They had no valvular, myocardial, or congenital heart disease. (8) Graded treadmill exercise tests were terminated because these patients experienced moderate or severe angina. (9) They were not taking digitalis compounds or diuretics. (10) They had significant coronary narrowing and significant ST segment depression after exercise. The definition of “significant” used in this report is described below. Those with significant ST segment elevation in leads II, III, aVF, or V, to V, after exercise were excluded. Informed consent was obtained from all patients. Coronary
of Internal
From The First Department School of Medicine. Received accepted
for publication June 20, 1985.
Feb.
Reprint requests: Isao Kubota, Medicine, Yamagata University 990-23. Japan.
Medicine,
25, 1985; revision
Yamagata received
May
M.D., The First Department School of Medicine, Zao-Iida,
University 20, 1985; of Internal Yamagata
arteriography
and
left
ventriculography.
Coronary arteriography was performed by means of the Judkins technique in multiple projections. Coronary artery narrowing of 70% or greater in luminal diameter was considered significant. Of 61 patients studied, 32 had one-vessel disease, 12 had two-, and 17 had three-vessel disease. Of 32 patients with one-vessel disease, 19 had left 949
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November, 1985 American Heart Journal
Kubota et al.
Fig. 1. Electrode sites on the body surface. Each ECG lead is represented by a dot. Eighty-seven lead points were arranged lattice like (13 x ‘7 matrix), except for four lead points in both midaxillary regions, and covered the entire thoracic surface. Columns A, E, and I were positioned in the right midaxillary, midsternal, and left midaxillary lines, respectively. Columns B-D and F-H were evenly spaced between columns A-E and E-I, respectively. Column J was located so as to make the distance between columns I and J equal to that between H and 1. Column M was located similarly. Columns K and L were evenly spaced between columns J and M. Lead points E, and E, were located on the second and fifth intercostal spaces, respectively. Row 5 was located equidistant between rows 6 and 4. Rows 7 and 3-l were located so as to make the distance between adjacent rows equal. anterior descending artery (LAD) disease, six had left circumflex artery (LCX) disease, and seven had right coronary artery (RCA) disease. All six patients with LCX disease had a right dominant coronary artery. Of the seven patients with RCA disease, four had right predominant, one had left predominant, and two had a balanced pattern of coronary distribution. Biplane left ventriculograms in the 30-degree right anterior oblique and 60-degree left anterior oblique projections were recorded on 35 mm film taken at 50 frames/ set with a Toshiba B-inch image amplifier system (Angiorex/U-arm). Left ventricular wall motion was evaluated according to the reporting system of the American Heart Association on patients evaluated for coronary artery disease.6 Body surface mapping and treadmill exercise testing. Graded treadmill exercise tests were performed according to the Bruce protocol. All medication was stopped at least 24 hours before testing. Eighty-seven-lead ECG mapping was performed before and 1.5 and 5 minutes after exercise by means of a previously described technique.7l8 Body surface mapping was performed with the use of the HPM-5100 system (Chunichi Denshi Company, Nagoya).g Eighty-seven electrodes were placed over the torso, 59 leads on the anterior chest, and 28 on the back. The data were recorded in digital format, using Wilson’s central terminal as a reference, at a rate of 250 samples/set. Data sampling was always done at the resting expiratory level in the supine position. The lead points of body surface mapping are shown in Fig. 1. The vertical lines of A, E, and I are on the right midaxillary, midsternal, and left midaxillary lines, respectively. Lead points E, and E, were
2
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1
~--f~~+--t-+-+--+-+-+-~+A
nlmv
BCDEFGHIJ
B. 1.5 min after
K
L
M
exercise
_____ 1
-r--T-&-t^q++++4--A-.~.......--.~-~-.--~.~....~.----.-----~ A
BCDEFGHIJKLM
Fig. 2. ECG waveforms of all 87 leads both before CA) and I.5 minutes after (B) exercise from a patient with three-vessel disease. ST segment depression was observed around the left anterior and lateral chest, and ST segment elevation was found on the right upper anterior chest and right upper anterior back. located on the level of the second and fifth intercostal spaces, respectively. Lead points Gq, H1, and I, correspond to V,, V,, and V, of the standard 12-ECG, respectively. Each lead of the ECG was analyzed for significant ST segment changes: 0.05 mV or greater horizontal or downsloping ST segment depression below the baseline, lasting 0.08 seconds; and 0.05 mV or greater horizontal or upsloping ST segment elevation above the baseline, lasting 0.08 seconds. The amplitude of the ST segment was measured at 0.04 seconds after the J point. In this study, we used the number of lead points that showed ST segment depression (nSTd) and the number of those that showed ST segment elevation (nSTe) as the indices of the extent of exerciseinduced ST segment changes on the body surface. Statistical analysis. The correlation between nSTd and nSTe was assessed by means of the least-squares method
Volume 110 Number 5
ST mapping
after
exercise
in effort
. .
15, a, :,c
. 10L .. . U. n .
5 Fig. 3. Body surface distributions of ST segment changes in all 61 patients 1.5 minutes after exercise. Dotted and shaded areas indicate the areas of ST segment depression and ST segment elevation, respectively. The numerals in the figure represent the number of patients who developed ST segment changes at each lead point.
of linear regression analysis to determine the correlation coefficient.
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Fig. 4. Correlation between nSTd and nSTe 1.5 minutes after exercise in all 61 patients. There was good correlation between them (r = 0.92). nSTd = number of lead points that developed ST segment depression; nSTe = number of lead points that developed ST segment elevation.
RESULTS Representative case. Fig. 2 shows all 87 ECG waveforms both before and 1.5 minutes after exercise in one patient with three-vessel disease. The leads which developed ST segment depression after exercise are surrounded by a broken line and those with ST segment elevation are surrounded by solid lines. This patient had both ST segment depression and ST segment elevation 1.5 minutes after exercise. The area of ST segment depression was observed around the left anterior and lateral chest, and the area of ST segment elevation was found on the right upper anterior chest and right upper back. Body surface distributions of ST changes. Exerciseinduced ST segment changes 1.5 minutes after exercise were analyzed in individual patients. All 61 patients had exercise-induced ST segment depression in at least one of the 87 leads as mentioned previously (see Methods). Of the 61 patients, 16 had ST segment depression without simultaneous ST segment elevation and 45 had ST segment depression with concomitant ST segment elevation. Fig. 3 shows the body surface distributions of ST segment changes in all 61 patients. The dotted and shaded areas indicate the areas of ST segment depression and ST segment elevation, respectively. The numerals in the figure represent the number of patients who developed ST segment changes at each lead point. There was no overlap between the areas of ST segment depression and ST segment elevation. ST segment depression occurred most frequently in the left anterior chest leads, especially in lead Hq, that is, V, of the standard 1Zlead ECG. In this lead, 53 patients (87%) developed ST segment depression.
In contrast, ST segment depression occurred exclusively outside the conventional precordial leads V, to V, in 6 (10% ) of the 61 patients. Of these six patients, five had one-vessel disease and one had two-vessel disease. None of the patients developed ST segment depression in leads on the right back or right upper anterior chest. ST segment elevation mainly occurred in leads on the right upper anterior chest and right upper back. Of the 45 patients who developed ST segment elevation, 39 (87%) had ST segment elevation at lead C,. None of the patients developed ST segment elevation in leads on the left anterior chest and lower thoracic surface. Relationship between sion. The relationship
ST elevation
and ST depres-
between nSTd and nSTe 1.5 minutes after exercise was investigated for individual patients (Fig. 4). There was a good correlation between them (r = 0.92). Five minutes after exercise, we could not detect significant ST segment changes in 22 of the 61 patients. Of the remaining 39 patients, 10 had ST segment depression without simultaneous ST segment elevation and 29 patients had ST segment depression with concomitant ST segment elevation. ST segment elevation without ST segment depression was not observed in any patient. In these 39 patients, we correlated changes in nSTd and changes in nSTe from 1.5 minutes to 5 minutes after exercise for individual patients (Fig. 5). A good correlation was observed between them (r = 0.89). ST changes in one-vessel disease. The spatial distributions of ST segment changes in each one-vessel disease (LAD, LCX, and RCA diseases) were compared 1.5 minutes after exercise (Figs. 6 and 7). Fig.
952
Kubota
November. 1985 American Heart Journal
et al.
r=0.89
I
p
1
y=o.53x-0.35
//y
-20 I I
-30
A -20
0
-10
changes
in
0
CDEFGHIJKLM
10
nSTd
Fig. 5. Correlation between changes in nSTd and nSTe from 1.5 to 5 minutes after exercise in the 39 patients who still had ST segment changes 5 minutes after exercise. There was good correlation between them (r = 0.89). nSTd = number of lead points that developed ST segment depression; nSTe = number of lead points that developed ST segment elevation.
6 shows the body surface distributions of ST segment changes in each group. The dotted and shaded areas indicate the areas of ST segment depression and ST segment elevation, respectively. The numerals in the figure represent the number of patients who developed ST segment changes at each lead point. Patients with RCA disease tended to have ST segment depression in more lower leads compared with those with LAD disease. However, there was considerable overlap in the sites of ST segment depression among the three groups. Fig. 7 depicts the locations of the electrode with maximal degree of ST segment depression in patients with one-vessel disease. The arrows indicate the five patients who developed ST segment depression exclusively outside the conventional precordial leads. In the 13 patients with RCA or LCX disease, two patients with balanced circulation are denoted by the letter B and one with left dominant circulation by the letter L. The other 10 patients had right dominant coronary circulation. There was also the tendency for patients with RCA disease to have the locations of maximal degree of ST segment depression at more lower leads than those with LAD disease. Among patients with RCA disease, patients with right predominant circulation tended to have the locations at more lower leads than patients with left predominant or balanced circulation. Overlap of the locations among the three groups (LAD, LCX, and RCA diseases) was also widely observed.
6. Body surface distributions of exercise-induced ST segment changes in each one-vessel disease 1.5 minutes after exercise. Although patients with right coronary artery (RCA) disease tended to have ST segment depression in more lower leads than those with left anterior descending artery (LAD) disease, there was considerable overlap in the sites of ST segment depression among the three groups. LCX = left circumflex artery. Display format as in Fig. 3. Fig.
DISCUSSION
In the present study, we investigated the body surface distribution patterns of exercise-induced ischemic ST segment changes on the entire thoracic surface in effort angina pectoris without myocardial infarction. This information has important clinical implications in interpreting the results of exercise tests because at present ischemic ST segment changes are the most reliable and widely used ECG markers of myocardial ischemia. Body surface distributions of ST changes. ST segment depression was most frequently seen in the left anterior ‘chest leads. The classic study of Blackburn and Katigbak’O concluded that the most sensitive lead of the standard 12-ECG was V,. We demonstrated in our study that on the entire thoracic surface the V, electrode site is also the most sensitive unipolar electrode position for detecting ischemic ST segment depression. In six patients (lo%), standard precordial leads V, to V, could not sample the ischemic ST segment depression. This finding is compatible with that of Fox et al.,4 who reported that 9 (7% 1 of 122 patients without ST segment depression in the standard precordial leads had ST segment depression at some sites on a 164ead precordial grid. In our study, five of six patients had one-vessel disease. Therefore, ECG mapping may be useful for improving the sensitivity of exercise testing particularly in one-vessel disease. ST segment elevation was most often seen around
Volume 110 Number 5
the right upper anterior chest. The most sensitive lead for detecting ST segment elevation was CT, the position of which was just below the right clavicle on the midclavicular line. These observations indicate that the most sensitive bipolar lead for detecting ST segment changes in exercise testing is the lead which represents a difference in electrical potential between leads C, and V,. They also indicate that bipolar lead C, to V, is the most sensitive for detecting ST segment depression among various lead systems including unipolar lead V,. We thus recommend the use of bipolar lead C7 to V, for the diagnosis of myocardial ischemia in exercise ECGs. Clinical significance of ST elevation. Transient ST segment elevation during exercise testing has been observed at the sites of a ventricular aneurysm or a previous myocardial infarction.“-‘” In the absence of these conditions, exercise-induced ST segment elevation may develop in some patients with variant angina or angina at rest.14-** We excluded patients with a previous myocardial infarction, variant angina pectoris, or angina at rest and investigated the body surface distributions of exercise-induced ST segment changes in patients with stable effort angina pectoris. There was no overlap between areas of ST segment depression and ST segment elevation in our study population. None of the patients developed ST segment depression in leads on the right upper anterior chest or upper back, and none developed ST segment elevation on the left anterior chest or lower thoracic surface. It was generally believed that exercise-induced ST segment depression is a reflection of the subendocardial ischemia of the left ventricle. From the occupying position on the thoracic surface, it was suggested that the sites which showed ST segment elevation face the interior of the left ventricle and the ST segment elevation observed in this study directly reflects the subendocardial ischemia of the left ventricle. This concept was confirmed by the fact that a good correlation was found between nSTe and nSTd. Furthermore, changes in nSTe for individual patients after the cessation of exercise were proportional to similar changes in nSTd. Sixteen (26%) of the 61 patients studied had ST segment depression without concomitant ST segment elevation. These patients had relatively few lead points of ST segment depression (mean 4.8 leads). The distance from the left ventricle is longer in leads on the right upper chest than in leads on the left anterior chest. Thus, in these patients, subendocardial ischemia of the left ventricle producing ST segment depression in the left anterior chest leads was thought to be inadequate to produce ST seg-
ST mapping
after
exercise
in effort
angina
953
LAD h=19)
7 6 5 L 3 2 1 ABCDEFGHIJKLM
LCX (n=6)
7
RCA (n=7)
6 5 L 3
f
2 1
L-A
0
C
DEFGHIJKLM
Fig. 7. Locations of the electrode with maximal degree of ST segment depression in patients with one-vessel disease of the left anterior descending artery (LAD), left circumflex artery (LCX), and right coronary artery (RCA) 1.5 minutes after exercise. Numbers in parentheses represent number of patients. Arrows indicate patients who developed ST segment depression exclusively outside the conventional precordial leads. In 13 patients with RCA disease or LCX disease, two patients with balanced coronary circulation are denoted by a B and one with left dominant circulation by an L. Although there was a tendency for patients with RCA disease to have the locations at more lower leads than those with LAD disease, overlap of the locations among the three groups was widely observed.
ment elevation in the right upper chest leads. Dunn et al.” concluded that during K&lead exercise ECGs, ST segment elevation in V, and/or aV, in the absence of anterior Q waves predicts LAD disease. LAD disease was present in 38 of 46 patients (83 % ) with V,/aV, ST segment elevation and in 72 of 144 patients (50%) without V,/aV, ST segment elevation. In 35 of the 46 patients with ST segment elevation in Vl/aVi,, it was associated with ST segment depression in other leads. We also found that all 11 patients with ST segment elevation in lead D5, corresponding approximately to V1, had LAD disease, although the prevalence of LAD disease was relatively high in our study population (48 of 61, 79%). We believe from our results that ST segment elevation in V, in effort angina pectoris
954
Kubota
November, 1985 American Heart Journal
et al.
mainly represents the severe subendocardial ischemia rather than the transmural ischemia of the left ventricle. In fact, 11 patients with ST segment elevation in lead D, (near V,) had more leads of ST segment depression than 50 patients without such ST segment elevation (mean * SD, 26.0 f 3.6 vs 12.9 + 7.9 leads, p < 0.01). ST changes in one-vessel disease. With the use of 12-lead exercise ECGs, Dunn et a120 with Fuchs et a1.21reported that the site of ST segment depression on exercise did not identify the anatomic site of coronary artery obstruction. Recently, Abouantoun et al.22 reported that the sites of exercise-induced thallium-201 scintigraphic defects could not be specifically identified by exercise-induced ST vector shifts in 54 patients with coronary artery disease. They found that the majority of patients had ST vectors extending during exercise into the right upper direction. In contrast, Fox et a1.3 used 16-lead precordial mapping after exercise and postulated that isolated disease of LAD, LCX, or RCA was present when ST segment changes were confined to the anterior, lateral, and inferior regions of the left hemithorax, respectively. They reported that typical precordial projections of ST segment changes were found in 14 (82 % ) of the 17 patients with one-vessel disease and with ST segment changes on 16-lead mapping (eight of them showed no ST segment changes in the modified 12-lead ECG). Although, in our observations, patients with RCA disease tended to have ST segment depression in more lower leads than those with LAD disease, there was considerable overlap in the sites of ST segment depression among patients with LAD disease, those with LCX disease, and those with RCA disease. This result indicated that the body surface distribution pattern of ST segment depression was not simply determined by the anatomic site of coronary stenosis. The lack of a clear correlation between the location of exercise-induced ST segment depression and the site of coronary stenosis may be related to various factors. These include the presence or absence of collateral circulation, individual differences of coronary artery anatomy,23 and individual differences in heart position in relation to the electrode positions. One plausible explanation is that exercise-induced ischemia in patients with effort angina pectoris extends from a region supplied by a stenotic vessel to surrounding regions and is prone to take the form of global subendocardial ischemia (e.g., because of elevated left ventricular end-diastolic pressure). Accordingly, the left ventricular apex may be most vulnerable by myocardial ischemia. This is in agreement with the fact that
exercise-induced ST segment depression is most often seen in left anterior chest leads not only in the total study population but also in patients with each one-vessel disease. However, the possibility of predicting the obstructed artery by means of body surface mapping during exercise testing should be further evaluated with a large number of patients and with ECG changes in addition to the ischemic ST segment changes used in this study. The authors express their gratitude to Professor Kozui Miyazawa for his valuable help in this study. REFERENCES
1. 2.
3.
4.
5.
6.
7.
8.
9.
Fortuin NJ, Weiss JL: Exercise stress testing. Circulation 56:699, 1977. Fox KM, Selwyn AP, Shillingford JP: A method for precordial surface mapping of the exercise electrocardiogram. Br Heart J 40:1339, 1978. Fox KM, Selwyn A, Oakley D, Shillingford JP: Relation between the precordial projection of S-T segment changes after exercise and coronary angiographic findings. Am J Cardiol 44:1068, 1979. Fox KM, Deanfield J, Ribero P, England D, Wright C: Projection of ST segment changes on to the front of the chest. Practical implications for exercise testing and ambulatory monitoring. Br Heart J 48:555, 1982. Fox KM, Jonathan A, Selwyn A: Significance of exerciseinduced ST segment elevation in patients with previous myocardial infarction. Br Heart J 49:15, 1983. 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 5 1:5, 1975. Kubota I, Saito K, Watanabe Y, Tsuiki K, Yasui S: Treadmill exercise test using body surface mapping. A quantitative diagnostic method for coronary artery disease. Jpn Heart J 22:871, 1981. Kubota I, Watanabe Y, Harada M, Kaminishi T, Tsuiki K, Yasui S: Treadmill stress test usine bodv surface mannina in coronary artery disease. The clinical” significance bf ST depression. Jpn Circ J 46:8, 1982. Watanabe T, Toyama J, Toyoshima H, Oguri H, Ohno M, Ohta T, Okajima M, Naito Y, Yamada K: A practical microcomputer based mapping system for body surface, precordium, and epicardium. Comput Biomed Res 14:341, 1981.
10. 11.
12.
13.
14.
15.
16.
17.
Blackburn H, Katigbak R: What electrocardiographic leads to take after exercise? AM HEART J 67:184, 1963. Dunn RF, Bailey IK, Uren R, Kelly DT: Exercise-induced ST-segment elevation. Correlation of thallium-201 myocardial perfusion scanning and coronary arteriography. Circulation 61:989, 1980. Gorlin R, Klein MD, Sullivan JM: Prospective correlative study of ventricular aneurysm. Mechanical concept and clinical recognition. Am J Med 42:512, 1967. Chahine RA, Raizner AE, Ishimori T: The clinical significance of exercise-induced ST-segment elevation. Circulation 54:209, 1976. Weiner DA, Schick EC, Hood WB, Rayan TJ: ST-segment elevation during recovery from exercise. A new manifestation of Prinzmetal’s variant angina. Chest 74:133, 1978. Yasue H, Omote S, Takizawa A, Nagao M, Miwa K, Tanaka S: Circadian variation of exercise capacity in patients with Prinzmetal’s variant angina. Role of exercise-induced coronary arterial spasm. Circulation 59:938, 1979. Waters DD. Chaitman BR, Dunras G, Theroux P, Mizgala HF: Coronary artery spasm during exercise in patients with variant angina. Circulation 59:580, 1979. Waters DD, Szlachcic J, Bourassa MG, Scholl JM, Theroux P: Exercise testing in patients with variant angina. Results,
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correlation with clinical and angiographic features and prognostic significance. Circulation 65:265, 1982. 18. Specchia G, Servi S, Falcone C, Angoli L, Mussini A, Bramucci E, Marioni GP, Ardissino D, Salerno J, Bobba P: Significance of exercise-induced ST-segment elevation in patients without myocardial infarction. Circulation 63:46, 1981. 19. Dunn RF, Freedman B, Kelly DT, Bailey IK, McLaughlin A: Exercise-induced ST-segment elevation in leads V, or aVL. A predictor of anterior myocardial ischemia and left anterior descending coronary artery disease. Circulation 63:1357, 1981. 20. Dunn RF, Freedman B, Bailey IK, Uren RF, Kelly DT: Localization of coronary artery disease with exercise electro-
mapping
after
exercise
in effort
angina
cardiography. Correlation with thallium-201 myocardial perfusion scanning. Am J Cardiol 48:837, 1981. 21. Fuchs RM, Achuff SC, Grunwald L, Yin FCP. Griffith LSC: Electrocardiographic localization of coronary artery narrowings. Studies during myocardial ischemia and infarction in patients with one-vessel disease. Circulation 66:1168, 1982. 22. Abouantoun S, Ahnve S, Savvides M, Witztum K, Jensen D, Froelicher V: Can areas of myocardial ischemia be localized by the exercise electrocardiogram? A correlative study with thallium-201 scintigraphy. AM HEART J 108:933, 1984. 23. Iskandrian AS, Legal BL: Structure and function of the coronary arteries. How are they related? Cathet Cardiovasc Diagn 5:101, 1979.
Arrhythmia inducibility and ventricular vulnerability in a chronic feline infarction
model
Ventricular tachyarrhythmias are the cause of sudden cardiac death in ischemic heart disease. Reliable animal models are necessary to study techniques for identifying individuals at risk and to develop effective modes of therapy. The purpose of the present study was to evaluate the inducibility of ventricular tachyarrhythmias and vulnerability to ventricular fibrillation and to correlate these findings with changes in ventricular refractoriness in a chronic feline model. Twelve conditioned cats were randomly divided into two groups: group A, sham-operated controls (n = 5); or group B, permanent occlusion of the left anterior descending coronary artery (n = 7). Two weeks later, the following measurements were made: (1) assessment of refractory periods at several ventricular sites; (2) inducibility to ventricular tachyarrhythmias; and (3) determination of ventricular fibrillation threshold. After electrophysiologic testing, the animals were killed and the hearts were studied histologically. Ventricular fibrillation thresholds were significantly lower in group B compared with group A (13 f 3 vs 46 + g mA; p < 0.01). One of the sham-operated controls had induction of nonsustained ventricular tachycardia, while six of the group B animals had reproducible, inducible ventricular tachyarrhythmias (p < 0.01). There was a significant dispersion in effective refractory periods between normal and infarcted sites in group B (46 i 6 msec) not seen in group A (12 f 2 msec, p < 0.01). The group A cats demonstrated minimal damage to the myocardium or cardiac architecture. Group B cats demonstrated extensive, transmural, homogeneous infarcts of approximately 30% of the anterior wall of the left ventricle. The chronically infarcted feline heart appears to be a reliable model to evaluate vulnerability to ventricular tachyarrhythmias. Moreover, temporal dispersion of refractoriness observed in infarcted animals, applicable to clinical measurement, may serve as a marker of chronic vulnerability. (AM HEART J 1 lO:g55, 1985.)
Lewis Wetstein, M.D., Raymond Mark, M.D., Gerald J. Kelliher, Ph.D., Ted Friehling, M.D., Kathleen M. O’Connor, M.S., and Peter R. Kowey, M.D. Richmond,
Vu., and Philadelphia,
From
of Thor&c and Cardiac Surgery, Medical College of Commonwealth University; and Departments of PatholMedicine, of Medical College of Pennsylvania.
Division
Virginia, Virginia ogy, Pharmacology,
Pa.
This work was supported in part by Grant No. G735A from the Southeastern Pennsylvania Chapter of the American Heart Association; Grant No. 648487 of the A. D. Williams Research Fund, Veterans Administration Research Advisory Award; by Grant 28903 from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.; and by a grant from the Coonrad Memorial Research Fund, Philadelphia, Pa. Work was performed during Dr. Wetstein’s tenure as a Special Investiga-
tor, the Southeastern Pennsylvania Chapter of the Association and Recipient of the Veterans Administration sory Award. Work was performed during Dr. Kowey’s Investigator. National Heart, Lung, and Blood Institute Institutes of Health. Received accepted
for publication June 10. 1985.
Feb. 25. 1985; revision
received
American Heart Research Advitenure as a New of the National May
Reprint requests: Lewis Wetstein, M.D., Associate Professor Division of Thoracic and Cardiac Surgery. Medical College P.O. Hex 68, MCV Station, Richmond, VA 23298.
13. 1985;
of Surgery, of Virginia,
955
Isao Kubota, M.D., Kozue Ikeda, M.D., Taketsugu Ohyama, M.D., Michiyasu Yamaki, M.D., Sukehiko Kawashima, M.D., Akira Igarashi, M.D., Kai Tsuiki, M.D., and Shoji Yasui, M.D. Yamugata, Japan
Ischemic ST segment changes (depression and elevation) are widely used indices for detection of myocardial ischemia in exercise testing.’ However, there are few data on body surface distribution patterns of ST segment changes2-5 because the number of lead points to detect such changes has been limited. These data are needed to clarify the clinical significance of ST segment changes in the diagnosis of coronary artery disease. The purpose of this study was to investigate the distribution patterns of exercise-induced ST segment changes on the body surface in effort angina pectoris without myocardial infarction by means of a body surface mapping technique. METHODS Study population. Of 506 consecutive patients who underwent treadmill exercise testing, using body surface mapping and coronary arteriography to assess coronary artery disease, 61 patients (45 men and 16 women)
satisfied all the following criteria and formed the study population: (1) The patients were between 41 and 72 (mean 58) years of age. (2) They were diagnosed as having stable effort angina pectoris. (3) They had no history of previous myocardial infarction established by typical chest pain, serum enzyme changes, and ECG findings. (4) They had no wall motion abnormalities such as akinesis or dyskinesis on left ventriculogram. (5) They had no intraventricular conduction disturbances or ST segment changes on resting 12-lead ECGs. (6) They had no clinical or ECG evidence of variant angina pectoris or spontaneous angina at rest. (7) They had no valvular, myocardial, or congenital heart disease. (8) Graded treadmill exercise tests were terminated because these patients experienced moderate or severe angina. (9) They were not taking digitalis compounds or diuretics. (10) They had significant coronary narrowing and significant ST segment depression after exercise. The definition of “significant” used in this report is described below. Those with significant ST segment elevation in leads II, III, aVF, or V, to V, after exercise were excluded. Informed consent was obtained from all patients. Coronary
of Internal
From The First Department School of Medicine. Received accepted
for publication June 20, 1985.
Feb.
Reprint requests: Isao Kubota, Medicine, Yamagata University 990-23. Japan.
Medicine,
25, 1985; revision
Yamagata received
May
M.D., The First Department School of Medicine, Zao-Iida,
University 20, 1985; of Internal Yamagata
arteriography
and
left
ventriculography.
Coronary arteriography was performed by means of the Judkins technique in multiple projections. Coronary artery narrowing of 70% or greater in luminal diameter was considered significant. Of 61 patients studied, 32 had one-vessel disease, 12 had two-, and 17 had three-vessel disease. Of 32 patients with one-vessel disease, 19 had left 949
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November, 1985 American Heart Journal
Kubota et al.
Fig. 1. Electrode sites on the body surface. Each ECG lead is represented by a dot. Eighty-seven lead points were arranged lattice like (13 x ‘7 matrix), except for four lead points in both midaxillary regions, and covered the entire thoracic surface. Columns A, E, and I were positioned in the right midaxillary, midsternal, and left midaxillary lines, respectively. Columns B-D and F-H were evenly spaced between columns A-E and E-I, respectively. Column J was located so as to make the distance between columns I and J equal to that between H and 1. Column M was located similarly. Columns K and L were evenly spaced between columns J and M. Lead points E, and E, were located on the second and fifth intercostal spaces, respectively. Row 5 was located equidistant between rows 6 and 4. Rows 7 and 3-l were located so as to make the distance between adjacent rows equal. anterior descending artery (LAD) disease, six had left circumflex artery (LCX) disease, and seven had right coronary artery (RCA) disease. All six patients with LCX disease had a right dominant coronary artery. Of the seven patients with RCA disease, four had right predominant, one had left predominant, and two had a balanced pattern of coronary distribution. Biplane left ventriculograms in the 30-degree right anterior oblique and 60-degree left anterior oblique projections were recorded on 35 mm film taken at 50 frames/ set with a Toshiba B-inch image amplifier system (Angiorex/U-arm). Left ventricular wall motion was evaluated according to the reporting system of the American Heart Association on patients evaluated for coronary artery disease.6 Body surface mapping and treadmill exercise testing. Graded treadmill exercise tests were performed according to the Bruce protocol. All medication was stopped at least 24 hours before testing. Eighty-seven-lead ECG mapping was performed before and 1.5 and 5 minutes after exercise by means of a previously described technique.7l8 Body surface mapping was performed with the use of the HPM-5100 system (Chunichi Denshi Company, Nagoya).g Eighty-seven electrodes were placed over the torso, 59 leads on the anterior chest, and 28 on the back. The data were recorded in digital format, using Wilson’s central terminal as a reference, at a rate of 250 samples/set. Data sampling was always done at the resting expiratory level in the supine position. The lead points of body surface mapping are shown in Fig. 1. The vertical lines of A, E, and I are on the right midaxillary, midsternal, and left midaxillary lines, respectively. Lead points E, and E, were
2
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1
~--f~~+--t-+-+--+-+-+-~+A
nlmv
BCDEFGHIJ
B. 1.5 min after
K
L
M
exercise
_____ 1
-r--T-&-t^q++++4--A-.~.......--.~-~-.--~.~....~.----.-----~ A
BCDEFGHIJKLM
Fig. 2. ECG waveforms of all 87 leads both before CA) and I.5 minutes after (B) exercise from a patient with three-vessel disease. ST segment depression was observed around the left anterior and lateral chest, and ST segment elevation was found on the right upper anterior chest and right upper anterior back. located on the level of the second and fifth intercostal spaces, respectively. Lead points Gq, H1, and I, correspond to V,, V,, and V, of the standard 12-ECG, respectively. Each lead of the ECG was analyzed for significant ST segment changes: 0.05 mV or greater horizontal or downsloping ST segment depression below the baseline, lasting 0.08 seconds; and 0.05 mV or greater horizontal or upsloping ST segment elevation above the baseline, lasting 0.08 seconds. The amplitude of the ST segment was measured at 0.04 seconds after the J point. In this study, we used the number of lead points that showed ST segment depression (nSTd) and the number of those that showed ST segment elevation (nSTe) as the indices of the extent of exerciseinduced ST segment changes on the body surface. Statistical analysis. The correlation between nSTd and nSTe was assessed by means of the least-squares method
Volume 110 Number 5
ST mapping
after
exercise
in effort
. .
15, a, :,c
. 10L .. . U. n .
5 Fig. 3. Body surface distributions of ST segment changes in all 61 patients 1.5 minutes after exercise. Dotted and shaded areas indicate the areas of ST segment depression and ST segment elevation, respectively. The numerals in the figure represent the number of patients who developed ST segment changes at each lead point.
of linear regression analysis to determine the correlation coefficient.
,-
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.
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Fig. 4. Correlation between nSTd and nSTe 1.5 minutes after exercise in all 61 patients. There was good correlation between them (r = 0.92). nSTd = number of lead points that developed ST segment depression; nSTe = number of lead points that developed ST segment elevation.
RESULTS Representative case. Fig. 2 shows all 87 ECG waveforms both before and 1.5 minutes after exercise in one patient with three-vessel disease. The leads which developed ST segment depression after exercise are surrounded by a broken line and those with ST segment elevation are surrounded by solid lines. This patient had both ST segment depression and ST segment elevation 1.5 minutes after exercise. The area of ST segment depression was observed around the left anterior and lateral chest, and the area of ST segment elevation was found on the right upper anterior chest and right upper back. Body surface distributions of ST changes. Exerciseinduced ST segment changes 1.5 minutes after exercise were analyzed in individual patients. All 61 patients had exercise-induced ST segment depression in at least one of the 87 leads as mentioned previously (see Methods). Of the 61 patients, 16 had ST segment depression without simultaneous ST segment elevation and 45 had ST segment depression with concomitant ST segment elevation. Fig. 3 shows the body surface distributions of ST segment changes in all 61 patients. The dotted and shaded areas indicate the areas of ST segment depression and ST segment elevation, respectively. The numerals in the figure represent the number of patients who developed ST segment changes at each lead point. There was no overlap between the areas of ST segment depression and ST segment elevation. ST segment depression occurred most frequently in the left anterior chest leads, especially in lead Hq, that is, V, of the standard 1Zlead ECG. In this lead, 53 patients (87%) developed ST segment depression.
In contrast, ST segment depression occurred exclusively outside the conventional precordial leads V, to V, in 6 (10% ) of the 61 patients. Of these six patients, five had one-vessel disease and one had two-vessel disease. None of the patients developed ST segment depression in leads on the right back or right upper anterior chest. ST segment elevation mainly occurred in leads on the right upper anterior chest and right upper back. Of the 45 patients who developed ST segment elevation, 39 (87%) had ST segment elevation at lead C,. None of the patients developed ST segment elevation in leads on the left anterior chest and lower thoracic surface. Relationship between sion. The relationship
ST elevation
and ST depres-
between nSTd and nSTe 1.5 minutes after exercise was investigated for individual patients (Fig. 4). There was a good correlation between them (r = 0.92). Five minutes after exercise, we could not detect significant ST segment changes in 22 of the 61 patients. Of the remaining 39 patients, 10 had ST segment depression without simultaneous ST segment elevation and 29 patients had ST segment depression with concomitant ST segment elevation. ST segment elevation without ST segment depression was not observed in any patient. In these 39 patients, we correlated changes in nSTd and changes in nSTe from 1.5 minutes to 5 minutes after exercise for individual patients (Fig. 5). A good correlation was observed between them (r = 0.89). ST changes in one-vessel disease. The spatial distributions of ST segment changes in each one-vessel disease (LAD, LCX, and RCA diseases) were compared 1.5 minutes after exercise (Figs. 6 and 7). Fig.
952
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November. 1985 American Heart Journal
et al.
r=0.89
I
p
1
y=o.53x-0.35
//y
-20 I I
-30
A -20
0
-10
changes
in
0
CDEFGHIJKLM
10
nSTd
Fig. 5. Correlation between changes in nSTd and nSTe from 1.5 to 5 minutes after exercise in the 39 patients who still had ST segment changes 5 minutes after exercise. There was good correlation between them (r = 0.89). nSTd = number of lead points that developed ST segment depression; nSTe = number of lead points that developed ST segment elevation.
6 shows the body surface distributions of ST segment changes in each group. The dotted and shaded areas indicate the areas of ST segment depression and ST segment elevation, respectively. The numerals in the figure represent the number of patients who developed ST segment changes at each lead point. Patients with RCA disease tended to have ST segment depression in more lower leads compared with those with LAD disease. However, there was considerable overlap in the sites of ST segment depression among the three groups. Fig. 7 depicts the locations of the electrode with maximal degree of ST segment depression in patients with one-vessel disease. The arrows indicate the five patients who developed ST segment depression exclusively outside the conventional precordial leads. In the 13 patients with RCA or LCX disease, two patients with balanced circulation are denoted by the letter B and one with left dominant circulation by the letter L. The other 10 patients had right dominant coronary circulation. There was also the tendency for patients with RCA disease to have the locations of maximal degree of ST segment depression at more lower leads than those with LAD disease. Among patients with RCA disease, patients with right predominant circulation tended to have the locations at more lower leads than patients with left predominant or balanced circulation. Overlap of the locations among the three groups (LAD, LCX, and RCA diseases) was also widely observed.
6. Body surface distributions of exercise-induced ST segment changes in each one-vessel disease 1.5 minutes after exercise. Although patients with right coronary artery (RCA) disease tended to have ST segment depression in more lower leads than those with left anterior descending artery (LAD) disease, there was considerable overlap in the sites of ST segment depression among the three groups. LCX = left circumflex artery. Display format as in Fig. 3. Fig.
DISCUSSION
In the present study, we investigated the body surface distribution patterns of exercise-induced ischemic ST segment changes on the entire thoracic surface in effort angina pectoris without myocardial infarction. This information has important clinical implications in interpreting the results of exercise tests because at present ischemic ST segment changes are the most reliable and widely used ECG markers of myocardial ischemia. Body surface distributions of ST changes. ST segment depression was most frequently seen in the left anterior ‘chest leads. The classic study of Blackburn and Katigbak’O concluded that the most sensitive lead of the standard 12-ECG was V,. We demonstrated in our study that on the entire thoracic surface the V, electrode site is also the most sensitive unipolar electrode position for detecting ischemic ST segment depression. In six patients (lo%), standard precordial leads V, to V, could not sample the ischemic ST segment depression. This finding is compatible with that of Fox et al.,4 who reported that 9 (7% 1 of 122 patients without ST segment depression in the standard precordial leads had ST segment depression at some sites on a 164ead precordial grid. In our study, five of six patients had one-vessel disease. Therefore, ECG mapping may be useful for improving the sensitivity of exercise testing particularly in one-vessel disease. ST segment elevation was most often seen around
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the right upper anterior chest. The most sensitive lead for detecting ST segment elevation was CT, the position of which was just below the right clavicle on the midclavicular line. These observations indicate that the most sensitive bipolar lead for detecting ST segment changes in exercise testing is the lead which represents a difference in electrical potential between leads C, and V,. They also indicate that bipolar lead C, to V, is the most sensitive for detecting ST segment depression among various lead systems including unipolar lead V,. We thus recommend the use of bipolar lead C7 to V, for the diagnosis of myocardial ischemia in exercise ECGs. Clinical significance of ST elevation. Transient ST segment elevation during exercise testing has been observed at the sites of a ventricular aneurysm or a previous myocardial infarction.“-‘” In the absence of these conditions, exercise-induced ST segment elevation may develop in some patients with variant angina or angina at rest.14-** We excluded patients with a previous myocardial infarction, variant angina pectoris, or angina at rest and investigated the body surface distributions of exercise-induced ST segment changes in patients with stable effort angina pectoris. There was no overlap between areas of ST segment depression and ST segment elevation in our study population. None of the patients developed ST segment depression in leads on the right upper anterior chest or upper back, and none developed ST segment elevation on the left anterior chest or lower thoracic surface. It was generally believed that exercise-induced ST segment depression is a reflection of the subendocardial ischemia of the left ventricle. From the occupying position on the thoracic surface, it was suggested that the sites which showed ST segment elevation face the interior of the left ventricle and the ST segment elevation observed in this study directly reflects the subendocardial ischemia of the left ventricle. This concept was confirmed by the fact that a good correlation was found between nSTe and nSTd. Furthermore, changes in nSTe for individual patients after the cessation of exercise were proportional to similar changes in nSTd. Sixteen (26%) of the 61 patients studied had ST segment depression without concomitant ST segment elevation. These patients had relatively few lead points of ST segment depression (mean 4.8 leads). The distance from the left ventricle is longer in leads on the right upper chest than in leads on the left anterior chest. Thus, in these patients, subendocardial ischemia of the left ventricle producing ST segment depression in the left anterior chest leads was thought to be inadequate to produce ST seg-
ST mapping
after
exercise
in effort
angina
953
LAD h=19)
7 6 5 L 3 2 1 ABCDEFGHIJKLM
LCX (n=6)
7
RCA (n=7)
6 5 L 3
f
2 1
L-A
0
C
DEFGHIJKLM
Fig. 7. Locations of the electrode with maximal degree of ST segment depression in patients with one-vessel disease of the left anterior descending artery (LAD), left circumflex artery (LCX), and right coronary artery (RCA) 1.5 minutes after exercise. Numbers in parentheses represent number of patients. Arrows indicate patients who developed ST segment depression exclusively outside the conventional precordial leads. In 13 patients with RCA disease or LCX disease, two patients with balanced coronary circulation are denoted by a B and one with left dominant circulation by an L. Although there was a tendency for patients with RCA disease to have the locations at more lower leads than those with LAD disease, overlap of the locations among the three groups was widely observed.
ment elevation in the right upper chest leads. Dunn et al.” concluded that during K&lead exercise ECGs, ST segment elevation in V, and/or aV, in the absence of anterior Q waves predicts LAD disease. LAD disease was present in 38 of 46 patients (83 % ) with V,/aV, ST segment elevation and in 72 of 144 patients (50%) without V,/aV, ST segment elevation. In 35 of the 46 patients with ST segment elevation in Vl/aVi,, it was associated with ST segment depression in other leads. We also found that all 11 patients with ST segment elevation in lead D5, corresponding approximately to V1, had LAD disease, although the prevalence of LAD disease was relatively high in our study population (48 of 61, 79%). We believe from our results that ST segment elevation in V, in effort angina pectoris
954
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November, 1985 American Heart Journal
et al.
mainly represents the severe subendocardial ischemia rather than the transmural ischemia of the left ventricle. In fact, 11 patients with ST segment elevation in lead D, (near V,) had more leads of ST segment depression than 50 patients without such ST segment elevation (mean * SD, 26.0 f 3.6 vs 12.9 + 7.9 leads, p < 0.01). ST changes in one-vessel disease. With the use of 12-lead exercise ECGs, Dunn et a120 with Fuchs et a1.21reported that the site of ST segment depression on exercise did not identify the anatomic site of coronary artery obstruction. Recently, Abouantoun et al.22 reported that the sites of exercise-induced thallium-201 scintigraphic defects could not be specifically identified by exercise-induced ST vector shifts in 54 patients with coronary artery disease. They found that the majority of patients had ST vectors extending during exercise into the right upper direction. In contrast, Fox et a1.3 used 16-lead precordial mapping after exercise and postulated that isolated disease of LAD, LCX, or RCA was present when ST segment changes were confined to the anterior, lateral, and inferior regions of the left hemithorax, respectively. They reported that typical precordial projections of ST segment changes were found in 14 (82 % ) of the 17 patients with one-vessel disease and with ST segment changes on 16-lead mapping (eight of them showed no ST segment changes in the modified 12-lead ECG). Although, in our observations, patients with RCA disease tended to have ST segment depression in more lower leads than those with LAD disease, there was considerable overlap in the sites of ST segment depression among patients with LAD disease, those with LCX disease, and those with RCA disease. This result indicated that the body surface distribution pattern of ST segment depression was not simply determined by the anatomic site of coronary stenosis. The lack of a clear correlation between the location of exercise-induced ST segment depression and the site of coronary stenosis may be related to various factors. These include the presence or absence of collateral circulation, individual differences of coronary artery anatomy,23 and individual differences in heart position in relation to the electrode positions. One plausible explanation is that exercise-induced ischemia in patients with effort angina pectoris extends from a region supplied by a stenotic vessel to surrounding regions and is prone to take the form of global subendocardial ischemia (e.g., because of elevated left ventricular end-diastolic pressure). Accordingly, the left ventricular apex may be most vulnerable by myocardial ischemia. This is in agreement with the fact that
exercise-induced ST segment depression is most often seen in left anterior chest leads not only in the total study population but also in patients with each one-vessel disease. However, the possibility of predicting the obstructed artery by means of body surface mapping during exercise testing should be further evaluated with a large number of patients and with ECG changes in addition to the ischemic ST segment changes used in this study. The authors express their gratitude to Professor Kozui Miyazawa for his valuable help in this study. REFERENCES
1. 2.
3.
4.
5.
6.
7.
8.
9.
Fortuin NJ, Weiss JL: Exercise stress testing. Circulation 56:699, 1977. Fox KM, Selwyn AP, Shillingford JP: A method for precordial surface mapping of the exercise electrocardiogram. Br Heart J 40:1339, 1978. Fox KM, Selwyn A, Oakley D, Shillingford JP: Relation between the precordial projection of S-T segment changes after exercise and coronary angiographic findings. Am J Cardiol 44:1068, 1979. Fox KM, Deanfield J, Ribero P, England D, Wright C: Projection of ST segment changes on to the front of the chest. Practical implications for exercise testing and ambulatory monitoring. Br Heart J 48:555, 1982. Fox KM, Jonathan A, Selwyn A: Significance of exerciseinduced ST segment elevation in patients with previous myocardial infarction. Br Heart J 49:15, 1983. 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 5 1:5, 1975. Kubota I, Saito K, Watanabe Y, Tsuiki K, Yasui S: Treadmill exercise test using body surface mapping. A quantitative diagnostic method for coronary artery disease. Jpn Heart J 22:871, 1981. Kubota I, Watanabe Y, Harada M, Kaminishi T, Tsuiki K, Yasui S: Treadmill stress test usine bodv surface mannina in coronary artery disease. The clinical” significance bf ST depression. Jpn Circ J 46:8, 1982. Watanabe T, Toyama J, Toyoshima H, Oguri H, Ohno M, Ohta T, Okajima M, Naito Y, Yamada K: A practical microcomputer based mapping system for body surface, precordium, and epicardium. Comput Biomed Res 14:341, 1981.
10. 11.
12.
13.
14.
15.
16.
17.
Blackburn H, Katigbak R: What electrocardiographic leads to take after exercise? AM HEART J 67:184, 1963. Dunn RF, Bailey IK, Uren R, Kelly DT: Exercise-induced ST-segment elevation. Correlation of thallium-201 myocardial perfusion scanning and coronary arteriography. Circulation 61:989, 1980. Gorlin R, Klein MD, Sullivan JM: Prospective correlative study of ventricular aneurysm. Mechanical concept and clinical recognition. Am J Med 42:512, 1967. Chahine RA, Raizner AE, Ishimori T: The clinical significance of exercise-induced ST-segment elevation. Circulation 54:209, 1976. Weiner DA, Schick EC, Hood WB, Rayan TJ: ST-segment elevation during recovery from exercise. A new manifestation of Prinzmetal’s variant angina. Chest 74:133, 1978. Yasue H, Omote S, Takizawa A, Nagao M, Miwa K, Tanaka S: Circadian variation of exercise capacity in patients with Prinzmetal’s variant angina. Role of exercise-induced coronary arterial spasm. Circulation 59:938, 1979. Waters DD. Chaitman BR, Dunras G, Theroux P, Mizgala HF: Coronary artery spasm during exercise in patients with variant angina. Circulation 59:580, 1979. Waters DD, Szlachcic J, Bourassa MG, Scholl JM, Theroux P: Exercise testing in patients with variant angina. Results,
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correlation with clinical and angiographic features and prognostic significance. Circulation 65:265, 1982. 18. Specchia G, Servi S, Falcone C, Angoli L, Mussini A, Bramucci E, Marioni GP, Ardissino D, Salerno J, Bobba P: Significance of exercise-induced ST-segment elevation in patients without myocardial infarction. Circulation 63:46, 1981. 19. Dunn RF, Freedman B, Kelly DT, Bailey IK, McLaughlin A: Exercise-induced ST-segment elevation in leads V, or aVL. A predictor of anterior myocardial ischemia and left anterior descending coronary artery disease. Circulation 63:1357, 1981. 20. Dunn RF, Freedman B, Bailey IK, Uren RF, Kelly DT: Localization of coronary artery disease with exercise electro-
mapping
after
exercise
in effort
angina
cardiography. Correlation with thallium-201 myocardial perfusion scanning. Am J Cardiol 48:837, 1981. 21. Fuchs RM, Achuff SC, Grunwald L, Yin FCP. Griffith LSC: Electrocardiographic localization of coronary artery narrowings. Studies during myocardial ischemia and infarction in patients with one-vessel disease. Circulation 66:1168, 1982. 22. Abouantoun S, Ahnve S, Savvides M, Witztum K, Jensen D, Froelicher V: Can areas of myocardial ischemia be localized by the exercise electrocardiogram? A correlative study with thallium-201 scintigraphy. AM HEART J 108:933, 1984. 23. Iskandrian AS, Legal BL: Structure and function of the coronary arteries. How are they related? Cathet Cardiovasc Diagn 5:101, 1979.
Arrhythmia inducibility and ventricular vulnerability in a chronic feline infarction
model
Ventricular tachyarrhythmias are the cause of sudden cardiac death in ischemic heart disease. Reliable animal models are necessary to study techniques for identifying individuals at risk and to develop effective modes of therapy. The purpose of the present study was to evaluate the inducibility of ventricular tachyarrhythmias and vulnerability to ventricular fibrillation and to correlate these findings with changes in ventricular refractoriness in a chronic feline model. Twelve conditioned cats were randomly divided into two groups: group A, sham-operated controls (n = 5); or group B, permanent occlusion of the left anterior descending coronary artery (n = 7). Two weeks later, the following measurements were made: (1) assessment of refractory periods at several ventricular sites; (2) inducibility to ventricular tachyarrhythmias; and (3) determination of ventricular fibrillation threshold. After electrophysiologic testing, the animals were killed and the hearts were studied histologically. Ventricular fibrillation thresholds were significantly lower in group B compared with group A (13 f 3 vs 46 + g mA; p < 0.01). One of the sham-operated controls had induction of nonsustained ventricular tachycardia, while six of the group B animals had reproducible, inducible ventricular tachyarrhythmias (p < 0.01). There was a significant dispersion in effective refractory periods between normal and infarcted sites in group B (46 i 6 msec) not seen in group A (12 f 2 msec, p < 0.01). The group A cats demonstrated minimal damage to the myocardium or cardiac architecture. Group B cats demonstrated extensive, transmural, homogeneous infarcts of approximately 30% of the anterior wall of the left ventricle. The chronically infarcted feline heart appears to be a reliable model to evaluate vulnerability to ventricular tachyarrhythmias. Moreover, temporal dispersion of refractoriness observed in infarcted animals, applicable to clinical measurement, may serve as a marker of chronic vulnerability. (AM HEART J 1 lO:g55, 1985.)
Lewis Wetstein, M.D., Raymond Mark, M.D., Gerald J. Kelliher, Ph.D., Ted Friehling, M.D., Kathleen M. O’Connor, M.S., and Peter R. Kowey, M.D. Richmond,
Vu., and Philadelphia,
From
of Thor&c and Cardiac Surgery, Medical College of Commonwealth University; and Departments of PatholMedicine, of Medical College of Pennsylvania.
Division
Virginia, Virginia ogy, Pharmacology,
Pa.
This work was supported in part by Grant No. G735A from the Southeastern Pennsylvania Chapter of the American Heart Association; Grant No. 648487 of the A. D. Williams Research Fund, Veterans Administration Research Advisory Award; by Grant 28903 from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.; and by a grant from the Coonrad Memorial Research Fund, Philadelphia, Pa. Work was performed during Dr. Wetstein’s tenure as a Special Investiga-
tor, the Southeastern Pennsylvania Chapter of the Association and Recipient of the Veterans Administration sory Award. Work was performed during Dr. Kowey’s Investigator. National Heart, Lung, and Blood Institute Institutes of Health. Received accepted
for publication June 10. 1985.
Feb. 25. 1985; revision
received
American Heart Research Advitenure as a New of the National May
Reprint requests: Lewis Wetstein, M.D., Associate Professor Division of Thoracic and Cardiac Surgery. Medical College P.O. Hex 68, MCV Station, Richmond, VA 23298.
13. 1985;
of Surgery, of Virginia,
955