- Email: [email protected]
Evaluation of isoproterenol as a method of stress testing
Evabation testing*
of isoproterenol
as a method
of stress
Darrel T. Combs, M.D., Major, MC, USA** Carroll M. Martin, M.D., Major, MC, USA*** San Francisco, Califi
Selective coronary arteriography has greatly enhanced the cardiologist’s ability to arrive at an anatomic diagnosis of coronary artery disease. There still exists, however, the need for a screening test, applicable in the outpatient setting, which can be applied safely and readily to a larger population. Recently, Wexler, Juaita, and Simonson’ have described, in a preliminary report, the use of isoproterenol as a method of stress testing. The purpose of our study was to evaluate further the isoproterenol stress test in a group of patients undergoing diagnostic coronary arteriography and to compare its specificity and sensitivity to that of a standard treadmill exercise test. Methods
Thirty-five patients who were scheduled for coronary arteriography and who met the following criteria were studied: (1) the resting la-lead electrocardiogram (ECG) did not reveal evidence of S-T segment depression; (2) they did not clinically or on ECG have evidence of ventricular hypertrophy, recent myocardial infarction, or conduction abnormalities; and (3) they had not taken any cardiac medications at least 48 hours before testing.
From Army Received Reprint Medical
the Cardiology Medical Center,
Service, Department San Francisco.
for publication requests Center,
Aug.
Cardiology
Service,
Letterman
***Formerly Staff, Cardiology Center, and presently assigned Tacoma. Wash.
Letterman
28, 1973.
to: Technical Publications Presidio of San Francisco,
*The opinions or assertions contained the authors and are not to be construed views of the Department of the Army **Staff,
of Medicine,
Editor, Letterman Calif. 94129.
Army
herein are the private views of as official or as reflecting the or the Department of Defense. Army
Medical
Service, Letterman Madigan Army
June, 1974, Vol. 87, No. 6, pp. 711-715
Center. Army Medical
Medical Center,
All tests were done in the postabsorptive state. The sequence of testing was determined by randomization. With 20 patients, the isoproterenol test was done first and with 15 patients the treadmill exercise test was the first test performed. The second test was performed after return to baseline of the patient’s heart rate, blood pressure, and ECG, or on the following day. Coronary arteriography was done within the next several days following stress testing. The isoproterenol test was performed as follows: (1) a control ECG was done before and after infusion of 20 to 50 c.c. of 6 per cent glucose in water; (2) isoproterenol in a concentration of 0.2 mg. per 100 C.C.of dextrose and water was infused at a rate of 1 to 2 lug per minute with constant ECG monitoring of precordial Lead V, or V, until diagnostic S-T segment depression developed, significant chest pain occurred, or a heart rate equal to at least 130 beats per minute was reached; and (3) ECG Leads I, II, III, aVL, aV,, and V, through V, were monitored immediately after infusion and every two minutes for 8 to 10 minutes. The graded exercise test was (1) initiated with a warm-up period of three minutes at a speed of one mile per hour and a 10 per cent grade; (2) the speed was then increased by 0.5 miles per hour every three minutes, maintaining a grade of 10 per cent until a speed of four miles per hour was reached; (3) the speed was then maintained at four miles per hour and the grade was increased by 2.5 per cent every three minutes; (4) the test was terminated when exhaustion occurred such that the patient was unable to continue, diagnostic S-T segment depression developed, or significant chest pain occurred, and (5) Leads V, or V, were monitored during exercise and Leads I, II, III, aV,, aV,, and V, through V, were
American
Heart Journal
711
Combe and Martin
I. Results of treadmill isoproterenol tests
Table
Tests Positive treadmill exercise test Negative treadmill exercise test Positive isoproterenol test Negative isoproterenol test
Normul patients (Total = 15)
exercise
and
Coronary artery disease patients (Total = 20)
1
10
14
10
3
12
12
8
monitored immediately after exercise and every two minutes for 8 to 10 minutes. The criteria used for either a positive treadmill or isoproterenol test was a flat or downward depression of the S-T segment of at least 1.0 mm. and lasting at least 0.08 second. Coronary arteriography was performed by the standard Judkins technique with multiple views of each coronary artery and both cineangiographic and fixed-film recording. A significant coronary lesion was defined as an obstruction seen on at least two views which resulted in 50 per cent or greater narrrowing of the coronary arterial lumen. The treadmill and isoproterenol tests were read by the authors without prior knowledge of the results of the coronary arteriography. Results Thirty-five patients were studied by coronary arteriography and 15 patients were judged to have normal coronary arteries while 20 patients had significant coronary artery disease. The average age of the patients with coronary artery disease was 48 years. There were 19 men and one woman. The patients with normal coronary arteries had an average age of 43.2 years and 13 of the 15 patients were men. The average heart rate with exercise testing was 152 beats per minute and with isoproterenol testing 141 beats per minute. The results of the treadmill exercise and isoproterenol tests are summarized in Table I. The isoproterenol test correctly predicted in 71 per cent of the patients whether or not ar-
712
teriographic coronary artery disease would be found. The treadmill tests resulted in correct predictions for 68 per cent of the patients. There were ten (50 per cent) false-negative results and one false-positive result with the treadmill exercise test, while with the isoproterenol there were eight (40 per cent) false-negative results and three (20 per cent) false-positive results. Ninetythree per cent of patients with normal coronary arteriography had a normal treadmill exercise test, whereas only 80 per cent of patients with normal coronary arteriography had a normal isoproterenol test. The isoproterenol test correctly identified 60 per cent of the patients with positive coronary arteriography; whereas the treadmill test identified 50 per cent of the patients. The incidence of chest pain occurring during treadmill and isoproterenol testing is summarized in Table II. Discussion
Exercise in the form of the Master’s test and the graded exercise test has been widely applied as a means of assistance in the evaluation of ischemic heart disease.2v3 However, there are at times situations in which the exercise test cannot be readily used; for example, in the patient with limiting claudication, chronic lung disease, or other physical or psychological limitations which prohibit adequate exercise. The sensitivity and specificity of the exercise test has also limited its use as an ideal screening test.“-’ In addition, because of the required bodily movement during exercise a stable ECG tracing is sometimes difficult to obtain. Atria1 pacing has overcome this latter problem but has the disadvantage of requiring cardiac catheterization. The use of drugs as a means of stress testing was initially described by Levine, Ernstene, and Jacobsonswho used subcutaneous epinephrine as a means of inducing angina in a group of patients with clinically diagnosed coronary artery disease and they compared this group’s response to a small group of normal control subjects. Although they felt the test was helpful, they recognized the dangers of the procedure and a subsequent negative report by Katz, Hamburger, and Levg prevented its widespread use. In more recent years, various other drugs such as pitressin,lO ergonavine,” and dopamine l2 have been de-
June, 1974, Vol. 87, No. 6
Isoproterenol
Table II. Incidence
of chest pain occurring
during
treadmill
Normal patients Tests Poeitive Negative Total Positive Negative Total
treadmill treadmill ieoproterenol isoproterenol
With chest pain
Heart Journal
testing
Coronary artery disease patients Without chest pain
0
1
2 2
12 13 3 6
0 6 6
scribed as useful in the diagnosis of ischemic heart disease; however, none of these agents has gained widespread popularity. Isoproterenol is a beta-stimulator which acts on the heart to increase myocardial contractility and heart rate and thereby myocardial oxygen consumption is increased.13 The demand for oxygen during isoproterenol stimulation in a patient with coronary artery disease might be expected to be greater than could-be supplied by the coronary circulation and ischemia could develop. In this circumstance, it has been demonstrated that lactate metabolism is depressed or reversed which indicates anaerobic metabolism.14*16 This property of isoproterenol to increase myocardial oxygen demand significantly has suggested its use as a means of stress testing. In a preliminary report, Wexler, Juaita, and Simonson described isoproterenol testing in a group of patients with clinical coronary artery disease and in an agematched clinically normal group. They also administered isoproterenol to a younger clinically normal group. They reported that the isoproterenol test was useful in separating the group with clinical coronary disease from the control groups and in addition noted that frequently ischemic changes occurred in the ECG before the onset of chest pain, thus the test could be stopped before the occurrence of pain. They reported no significant complications. We have found that the isoproterenol test could be administered easily and no significant complications occurred although one patient did have transient A-V dissociation. We have tested another patient (not included in this series) who had a short burst of ventricular tachycardia
American
and isoproterenol
as a method of stress testing
9
With chest pain
Without chest pain
9 4
6
13
7
6 6 13
1
4 3
7
shortly after termination of the isoproterenol test but this converted spontaneously to normal sinus rhythm. No other significant arrhythmias have occurred and isoproterenol testing appears to be safe, although the experience with these two patients emphasizes to us that proper resuscitative equipment must be available when any form of stress testing is undertaken. In our study, the isoproterenol test compared favorably to the exercise treadmill test when presence or absence of coronary artery disease was subsequently determined by arteriography. The isoproterenol test correctly identified 71 per cent of the group and the treadmill test identified 68 per cent (both statistically significant at the 5 per cent level). The weakness found in both tests was the high incidence of false-negatives, i.e., patients with coronary artery disease by arteriography who had normal stress testing. In this respect, the isoproterenol test was slightly better, but neither test was dependable. When combined, the results were slightly better with 14 of the 20 patients with coronary artery disease being correctly identified The high incidence of false-negatives requires further analysis. It may be that an adequate stress was not achieved; e.g., the average heart rate reached was only 138 beats per minute with the treadmill test and 131 beats per minute with the isoproterenol test. The treadmill test was stopped because of chest pain in five instances and because the patient felt he could not continue in five instances. The isoproterenol test was terminated because of chest pain in six patients and because of heart rate reaching 160 beats per minute in two patients. When the heart rate of patients who had
713
Combs
and
Martin
positive treadmill or isoproterenol tests is compared to the group that did not, it is seen that the heart rate was slightly slower in the former group (136 beats per minute for the treadmill test and 120.9 beats per minute for the isoproterenol test). Probably a more important factor in the incidence of false-negatives was the extent of coronary artery disease that was present in these patients. Six patients who had a negative treadmill test had only one vessel involved and only three patients who had a positive test had single coronary vessel disease. As previously reported in a paper from this institution,16 the incidence of false-negatives in patients with single-vessel disease was 65 per cent as compared to an overall false-negative incidence of 38 per cent (using 1.0 mm. S-T depression as the criterion for a positive test). In our small group of patients, the isoproterenol test was slightly better in identifying patients with single-vessel disease; five such patients were identified. It should also be appreciated that the criterion for coronary artery disease, i.e., coronary arteriography, is an anatomic test where the stress tests are dynamic tests and different information about the same disease process may be given by each. For example, the patient with a single coronary artery obstruction and a previous myocardial infarction may have eliminated the only area of &hernia and have a negative stress test, but he would show evidence of disease on coronary arteriography. It remains, however, that a negative treadmill exercise test cannot be taken as evidence that no coronary artery disease is present; this also appears to be true with the isoproterenol stress test. In contrast to the report of Wexler, Juaita, and Simonson,l our patients frequently developed chest discomfort with the infusion of isoproterenol; usually this was before the onset of S-T segment changes. The reason for the difference is unclear. We do recall from our earlier experience that two patients had prolonged pain apparently because the isoproterenol was infused too rapidly; however, even with much slower infusion, other patients have had pain. Chest discomfort developed both in those with and those without coronary artery disease and the occurrence of chest discomfort was of no value in separating the two groups (Table II). Ushiyama and co-worker&’ also noted a high incidence of chest pain with isoproterenol infusion. 714
Summary
Thirty-five patients undergoing diagnostic coronary arteriography were evaluated before catheterization by both a standard treadmill exercise test and by the intravenous infusion of isoproterenol in a concentration of 0.2 mg. per 100 C.C.of 5 per cent dextrose/water at a rate of 1 to 2 pg per minute. S-T segment depression of 1 mm. or greater of the ischemic type was considered to be a positive test. The isoproterenol test was comparable to the treadmill exercise test in predicting the presence or absence of coronary artery disease (71 per cent correct predictions with the isoproterenol test versus 68 per cent with the treadmill test) and was administered safely and easily. The isoproterenol test had several advantages: (1) the baseline is stable and the intraprocedure ECG can be more easily monitored; (2) the test can be applied in situations where exercise is impossible, for example, when a patient had severe claudication, incapacitating pulmonary disease, etc.; (3) other monitoring such as phonocardiograms, blood pressure, etc., can be easily obtained; and (4) cardiac catheterization is not required in contrast to stress by atria1 pacing. The isoproterenol test would appear to have a useful role in the clinical assessment of coronary artery disease. REFERENCES 1. Wexler, H., Juaita, J., and Simonson, E.: Electrocardiographic effects of isoprenaline in normal subjects and patients with coronary atherosclerosis, Br. Heart J. 33: 759,197l. 2. Bruce, R. A., and Hornstein, T. R.; Exercise stress testing in evaluation of patients with ischemic heart disease, Progr. Cardiovasc. Dis.11: 371, 1969. 3. Blomquist, C. G.: Use of exercise testing for diagnostic and functional evaluation of patients with arteriosclerotic heart disease, Circulation 54: 1120,197l. 4. Demany, M. D., Tambe, A., and Zimmerman, H. A.: Correlation between coronary arteriography and the postexercise electrocardiogram, Am. J. Cardiol. 19: 526, 1967. 5. Hultgren, H., Calciano, A., Platt, F., and Abrams, H.: A clinical evaluation of coronary arteriography, Am. J. Med. 42: 228, 1967. 6. Kasselbaum, D. G., Sutherland K. I., and Judkins, M. P.: A comparison of hypoxemia and exercise electrocardiography in coronary artery disease. Diagnostic precision of the methods correlated with coronary angiography, AM. HEART J. 75: 759,1968. 7. Roitman, D., Jones, W. B., and Sheffield, L. T.: Comparison of submaximal exercise ECG test with coronary cineangiocardiogram, Ann. Intern. Med. 172: 641, 1970. 8. Levine, S. A., Emstene, C. A., and Jacobson, B. M.: The use of epinephrine as a diagnostic test for angina pectoris, Arch. Intern. Med. 45: 191, 1930.
June, 1974, Vol. 87, No. 6
Isoproterenol as a method of stresstesting
9. Katz, L. N., Hamburger, W. W., and Lev, M.: The diagnostic value of epinephrine in angina pectoris, AM. HEART J. 7: 371,1932. 10. Raskin, A.: Pitressin test of coronary insufficiency, AM. HEART.~. 36: 567;1947. 11. Stein, I.: Observations on the action of ergonavine on the coronary circulation and its use in the diagnosis of coronary artery insufficiency, Am. HEART J. 37: 36, 1949. 12. Foresti, A.: Prospects for the diagnostic use of dooamine in coronm insufilciency, G. Ital. Cardiol. 1: 122,197l. 13. Kranson, N., Rolett, E. L., Yurchak, P. M., Hood, W. B., and Gorlin, R.: Isoproterenol and cardiovascular performance, Am. J. Med. 37: 514,1964.
American Heart Journal
14.
Kranson, N., and Gorlin, R.: Myocardial lactate metabolism in coronary insufilciency, Ann. Intern. Med. S9: 781,1963. 15. Cohen, L. S., Elliott, W. C., Klein, M. D., and Gorlin, R.: Coronary heart disease. Clinical, cinearteriographic, and metabolic correlations, Am. J. Cardiol. 17: 153, 1966. 16. Martin, C. M., and McConahay, D. R.: Maximal treadmill exercise electrocardiography. Correlations with coronary arteriography and cardiac hemodynamics, Circulation 46: 956, 1972. 17. Ushiyama, K., Kimura, E., Kikuchi, M., and Mabuchi, G.: Effects of nitroglycerin and propranolol on angina pectoris induced by intravenous infusion of isoproterenol, Isr. J. Med. Sci. 5: 736, 1969.
715
of isoproterenol
as a method
of stress
Darrel T. Combs, M.D., Major, MC, USA** Carroll M. Martin, M.D., Major, MC, USA*** San Francisco, Califi
Selective coronary arteriography has greatly enhanced the cardiologist’s ability to arrive at an anatomic diagnosis of coronary artery disease. There still exists, however, the need for a screening test, applicable in the outpatient setting, which can be applied safely and readily to a larger population. Recently, Wexler, Juaita, and Simonson’ have described, in a preliminary report, the use of isoproterenol as a method of stress testing. The purpose of our study was to evaluate further the isoproterenol stress test in a group of patients undergoing diagnostic coronary arteriography and to compare its specificity and sensitivity to that of a standard treadmill exercise test. Methods
Thirty-five patients who were scheduled for coronary arteriography and who met the following criteria were studied: (1) the resting la-lead electrocardiogram (ECG) did not reveal evidence of S-T segment depression; (2) they did not clinically or on ECG have evidence of ventricular hypertrophy, recent myocardial infarction, or conduction abnormalities; and (3) they had not taken any cardiac medications at least 48 hours before testing.
From Army Received Reprint Medical
the Cardiology Medical Center,
Service, Department San Francisco.
for publication requests Center,
Aug.
Cardiology
Service,
Letterman
***Formerly Staff, Cardiology Center, and presently assigned Tacoma. Wash.
Letterman
28, 1973.
to: Technical Publications Presidio of San Francisco,
*The opinions or assertions contained the authors and are not to be construed views of the Department of the Army **Staff,
of Medicine,
Editor, Letterman Calif. 94129.
Army
herein are the private views of as official or as reflecting the or the Department of Defense. Army
Medical
Service, Letterman Madigan Army
June, 1974, Vol. 87, No. 6, pp. 711-715
Center. Army Medical
Medical Center,
All tests were done in the postabsorptive state. The sequence of testing was determined by randomization. With 20 patients, the isoproterenol test was done first and with 15 patients the treadmill exercise test was the first test performed. The second test was performed after return to baseline of the patient’s heart rate, blood pressure, and ECG, or on the following day. Coronary arteriography was done within the next several days following stress testing. The isoproterenol test was performed as follows: (1) a control ECG was done before and after infusion of 20 to 50 c.c. of 6 per cent glucose in water; (2) isoproterenol in a concentration of 0.2 mg. per 100 C.C.of dextrose and water was infused at a rate of 1 to 2 lug per minute with constant ECG monitoring of precordial Lead V, or V, until diagnostic S-T segment depression developed, significant chest pain occurred, or a heart rate equal to at least 130 beats per minute was reached; and (3) ECG Leads I, II, III, aVL, aV,, and V, through V, were monitored immediately after infusion and every two minutes for 8 to 10 minutes. The graded exercise test was (1) initiated with a warm-up period of three minutes at a speed of one mile per hour and a 10 per cent grade; (2) the speed was then increased by 0.5 miles per hour every three minutes, maintaining a grade of 10 per cent until a speed of four miles per hour was reached; (3) the speed was then maintained at four miles per hour and the grade was increased by 2.5 per cent every three minutes; (4) the test was terminated when exhaustion occurred such that the patient was unable to continue, diagnostic S-T segment depression developed, or significant chest pain occurred, and (5) Leads V, or V, were monitored during exercise and Leads I, II, III, aV,, aV,, and V, through V, were
American
Heart Journal
711
Combe and Martin
I. Results of treadmill isoproterenol tests
Table
Tests Positive treadmill exercise test Negative treadmill exercise test Positive isoproterenol test Negative isoproterenol test
Normul patients (Total = 15)
exercise
and
Coronary artery disease patients (Total = 20)
1
10
14
10
3
12
12
8
monitored immediately after exercise and every two minutes for 8 to 10 minutes. The criteria used for either a positive treadmill or isoproterenol test was a flat or downward depression of the S-T segment of at least 1.0 mm. and lasting at least 0.08 second. Coronary arteriography was performed by the standard Judkins technique with multiple views of each coronary artery and both cineangiographic and fixed-film recording. A significant coronary lesion was defined as an obstruction seen on at least two views which resulted in 50 per cent or greater narrrowing of the coronary arterial lumen. The treadmill and isoproterenol tests were read by the authors without prior knowledge of the results of the coronary arteriography. Results Thirty-five patients were studied by coronary arteriography and 15 patients were judged to have normal coronary arteries while 20 patients had significant coronary artery disease. The average age of the patients with coronary artery disease was 48 years. There were 19 men and one woman. The patients with normal coronary arteries had an average age of 43.2 years and 13 of the 15 patients were men. The average heart rate with exercise testing was 152 beats per minute and with isoproterenol testing 141 beats per minute. The results of the treadmill exercise and isoproterenol tests are summarized in Table I. The isoproterenol test correctly predicted in 71 per cent of the patients whether or not ar-
712
teriographic coronary artery disease would be found. The treadmill tests resulted in correct predictions for 68 per cent of the patients. There were ten (50 per cent) false-negative results and one false-positive result with the treadmill exercise test, while with the isoproterenol there were eight (40 per cent) false-negative results and three (20 per cent) false-positive results. Ninetythree per cent of patients with normal coronary arteriography had a normal treadmill exercise test, whereas only 80 per cent of patients with normal coronary arteriography had a normal isoproterenol test. The isoproterenol test correctly identified 60 per cent of the patients with positive coronary arteriography; whereas the treadmill test identified 50 per cent of the patients. The incidence of chest pain occurring during treadmill and isoproterenol testing is summarized in Table II. Discussion
Exercise in the form of the Master’s test and the graded exercise test has been widely applied as a means of assistance in the evaluation of ischemic heart disease.2v3 However, there are at times situations in which the exercise test cannot be readily used; for example, in the patient with limiting claudication, chronic lung disease, or other physical or psychological limitations which prohibit adequate exercise. The sensitivity and specificity of the exercise test has also limited its use as an ideal screening test.“-’ In addition, because of the required bodily movement during exercise a stable ECG tracing is sometimes difficult to obtain. Atria1 pacing has overcome this latter problem but has the disadvantage of requiring cardiac catheterization. The use of drugs as a means of stress testing was initially described by Levine, Ernstene, and Jacobsonswho used subcutaneous epinephrine as a means of inducing angina in a group of patients with clinically diagnosed coronary artery disease and they compared this group’s response to a small group of normal control subjects. Although they felt the test was helpful, they recognized the dangers of the procedure and a subsequent negative report by Katz, Hamburger, and Levg prevented its widespread use. In more recent years, various other drugs such as pitressin,lO ergonavine,” and dopamine l2 have been de-
June, 1974, Vol. 87, No. 6
Isoproterenol
Table II. Incidence
of chest pain occurring
during
treadmill
Normal patients Tests Poeitive Negative Total Positive Negative Total
treadmill treadmill ieoproterenol isoproterenol
With chest pain
Heart Journal
testing
Coronary artery disease patients Without chest pain
0
1
2 2
12 13 3 6
0 6 6
scribed as useful in the diagnosis of ischemic heart disease; however, none of these agents has gained widespread popularity. Isoproterenol is a beta-stimulator which acts on the heart to increase myocardial contractility and heart rate and thereby myocardial oxygen consumption is increased.13 The demand for oxygen during isoproterenol stimulation in a patient with coronary artery disease might be expected to be greater than could-be supplied by the coronary circulation and ischemia could develop. In this circumstance, it has been demonstrated that lactate metabolism is depressed or reversed which indicates anaerobic metabolism.14*16 This property of isoproterenol to increase myocardial oxygen demand significantly has suggested its use as a means of stress testing. In a preliminary report, Wexler, Juaita, and Simonson described isoproterenol testing in a group of patients with clinical coronary artery disease and in an agematched clinically normal group. They also administered isoproterenol to a younger clinically normal group. They reported that the isoproterenol test was useful in separating the group with clinical coronary disease from the control groups and in addition noted that frequently ischemic changes occurred in the ECG before the onset of chest pain, thus the test could be stopped before the occurrence of pain. They reported no significant complications. We have found that the isoproterenol test could be administered easily and no significant complications occurred although one patient did have transient A-V dissociation. We have tested another patient (not included in this series) who had a short burst of ventricular tachycardia
American
and isoproterenol
as a method of stress testing
9
With chest pain
Without chest pain
9 4
6
13
7
6 6 13
1
4 3
7
shortly after termination of the isoproterenol test but this converted spontaneously to normal sinus rhythm. No other significant arrhythmias have occurred and isoproterenol testing appears to be safe, although the experience with these two patients emphasizes to us that proper resuscitative equipment must be available when any form of stress testing is undertaken. In our study, the isoproterenol test compared favorably to the exercise treadmill test when presence or absence of coronary artery disease was subsequently determined by arteriography. The isoproterenol test correctly identified 71 per cent of the group and the treadmill test identified 68 per cent (both statistically significant at the 5 per cent level). The weakness found in both tests was the high incidence of false-negatives, i.e., patients with coronary artery disease by arteriography who had normal stress testing. In this respect, the isoproterenol test was slightly better, but neither test was dependable. When combined, the results were slightly better with 14 of the 20 patients with coronary artery disease being correctly identified The high incidence of false-negatives requires further analysis. It may be that an adequate stress was not achieved; e.g., the average heart rate reached was only 138 beats per minute with the treadmill test and 131 beats per minute with the isoproterenol test. The treadmill test was stopped because of chest pain in five instances and because the patient felt he could not continue in five instances. The isoproterenol test was terminated because of chest pain in six patients and because of heart rate reaching 160 beats per minute in two patients. When the heart rate of patients who had
713
Combs
and
Martin
positive treadmill or isoproterenol tests is compared to the group that did not, it is seen that the heart rate was slightly slower in the former group (136 beats per minute for the treadmill test and 120.9 beats per minute for the isoproterenol test). Probably a more important factor in the incidence of false-negatives was the extent of coronary artery disease that was present in these patients. Six patients who had a negative treadmill test had only one vessel involved and only three patients who had a positive test had single coronary vessel disease. As previously reported in a paper from this institution,16 the incidence of false-negatives in patients with single-vessel disease was 65 per cent as compared to an overall false-negative incidence of 38 per cent (using 1.0 mm. S-T depression as the criterion for a positive test). In our small group of patients, the isoproterenol test was slightly better in identifying patients with single-vessel disease; five such patients were identified. It should also be appreciated that the criterion for coronary artery disease, i.e., coronary arteriography, is an anatomic test where the stress tests are dynamic tests and different information about the same disease process may be given by each. For example, the patient with a single coronary artery obstruction and a previous myocardial infarction may have eliminated the only area of &hernia and have a negative stress test, but he would show evidence of disease on coronary arteriography. It remains, however, that a negative treadmill exercise test cannot be taken as evidence that no coronary artery disease is present; this also appears to be true with the isoproterenol stress test. In contrast to the report of Wexler, Juaita, and Simonson,l our patients frequently developed chest discomfort with the infusion of isoproterenol; usually this was before the onset of S-T segment changes. The reason for the difference is unclear. We do recall from our earlier experience that two patients had prolonged pain apparently because the isoproterenol was infused too rapidly; however, even with much slower infusion, other patients have had pain. Chest discomfort developed both in those with and those without coronary artery disease and the occurrence of chest discomfort was of no value in separating the two groups (Table II). Ushiyama and co-worker&’ also noted a high incidence of chest pain with isoproterenol infusion. 714
Summary
Thirty-five patients undergoing diagnostic coronary arteriography were evaluated before catheterization by both a standard treadmill exercise test and by the intravenous infusion of isoproterenol in a concentration of 0.2 mg. per 100 C.C.of 5 per cent dextrose/water at a rate of 1 to 2 pg per minute. S-T segment depression of 1 mm. or greater of the ischemic type was considered to be a positive test. The isoproterenol test was comparable to the treadmill exercise test in predicting the presence or absence of coronary artery disease (71 per cent correct predictions with the isoproterenol test versus 68 per cent with the treadmill test) and was administered safely and easily. The isoproterenol test had several advantages: (1) the baseline is stable and the intraprocedure ECG can be more easily monitored; (2) the test can be applied in situations where exercise is impossible, for example, when a patient had severe claudication, incapacitating pulmonary disease, etc.; (3) other monitoring such as phonocardiograms, blood pressure, etc., can be easily obtained; and (4) cardiac catheterization is not required in contrast to stress by atria1 pacing. The isoproterenol test would appear to have a useful role in the clinical assessment of coronary artery disease. REFERENCES 1. Wexler, H., Juaita, J., and Simonson, E.: Electrocardiographic effects of isoprenaline in normal subjects and patients with coronary atherosclerosis, Br. Heart J. 33: 759,197l. 2. Bruce, R. A., and Hornstein, T. R.; Exercise stress testing in evaluation of patients with ischemic heart disease, Progr. Cardiovasc. Dis.11: 371, 1969. 3. Blomquist, C. G.: Use of exercise testing for diagnostic and functional evaluation of patients with arteriosclerotic heart disease, Circulation 54: 1120,197l. 4. Demany, M. D., Tambe, A., and Zimmerman, H. A.: Correlation between coronary arteriography and the postexercise electrocardiogram, Am. J. Cardiol. 19: 526, 1967. 5. Hultgren, H., Calciano, A., Platt, F., and Abrams, H.: A clinical evaluation of coronary arteriography, Am. J. Med. 42: 228, 1967. 6. Kasselbaum, D. G., Sutherland K. I., and Judkins, M. P.: A comparison of hypoxemia and exercise electrocardiography in coronary artery disease. Diagnostic precision of the methods correlated with coronary angiography, AM. HEART J. 75: 759,1968. 7. Roitman, D., Jones, W. B., and Sheffield, L. T.: Comparison of submaximal exercise ECG test with coronary cineangiocardiogram, Ann. Intern. Med. 172: 641, 1970. 8. Levine, S. A., Emstene, C. A., and Jacobson, B. M.: The use of epinephrine as a diagnostic test for angina pectoris, Arch. Intern. Med. 45: 191, 1930.
June, 1974, Vol. 87, No. 6
Isoproterenol as a method of stresstesting
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