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Beta Blockers and the Sensitivity of the Thallium Treadmill Test
Beta Blockers and the sensitivity of the Thallium Treadmill Test* Gary}. Martin, M.D.;t Robert E. Henkin, M.D.,+ and Patrick J Scanlon, M.D. §
The effect beta blockers (BB)may have on the sensitivity of the thallium treadmill test (Th-TMT) is controversial. The purpose of this study was to test the hypothesis that BB decrease the sensitivity of the Th-TMT. 1\vo hundred three patients over a two-year periodwere identi6ed who satis6ed the following criteria. All had symptom-limited upright treadmill exercise tests with stress and redistribution thallium imaging, as well as coronary angiography within two months of the Th-TMT. or58 patients with CAD not on
BB, 52 had an abnormal Th-TMT scan (sensitivity 90 percent), In comparison, the sensitivity of the 'Ih- TMT scan in the 88 patients with CAD receiving BB was 76 percent (p
Thallium treadmill tests are frequently done to diagnose the presence and severity of coronary artery disease. Patients are often sent for this relatively expensive test while taking beta blockers without thought to what influence these drugs may have on the diagnostic utility of the test. In an effort to address this question, we reviewed the sensitivity of stress/redistribution thallium scans in 203 patients. Of these patients, 55 percent were on beta blockers at the time of their thallium treadmill test.
treadmill scan (sensitivity 90 percent). In comparison, the sensitivity of the thallium treadmill test scan in the 88 patients with coronary artery disease receiving beta blockers was 76 percent (p
METHODS
Over a two-year period, 203 patients were identi6ed at our medical center who satisfied the following criteria: (1) all had symptom limited upright treadmill exercise tests with stress and redistribution thallium imaging. (2) All patients also had coronary angiography within two months of the thallium treadmill test. Patients with any significant intervening clinical event, as well as any patient status post coronary artery bypass surgery were excluded. Coronary artery disease was defined as greater than or equal to 70 percent luminal diameter narrowing in one or more major arterial branches. In addition, detailed information was available for the last 122 consecutive patients, including severity of coronary artery disease, as well as use of concomitant drugs such as calcium channel blockers and long-acting nitrates. The chi-square test was used when comparing the sensitivity of the stress/rest thallium scan for diagnosing coronary artery disease as well as when assessing use of concomitant drugs. RESULTS
Of 58 patients with coronary artery disease not receiving beta blockers, 52 had an abnormal thallium *From the Department of Medicine, Northwestern University Medical School, Chicago, and the Departments of Medicine and Radiology, Loyola University Medical Center, Maywood, Illinois. tAssistant Professor of Medicine. *Professor of Radiology. 'Professor of Medicine. Manuscript received September 11; revision accepted March 23.
v.
DISCUSSION
A large randomized study evaluating the effects of beta blockers on the sensitivity of thallium scans is Table I-Severity ojCorontJ'l/ Artery DiBeaae* Severity of CAD
CADonBB, %
1 Vessel disease 2 Vessel disease 3 Vessel disease
32 39
Left main
CAD not on BB, % 25 33 36
24
6
5
*Abbreviations: CAD, coronary artery disease; BB, beta blocker.
Table 2-Concomitant Drug Therapy* Concomitant Drug
CAD on BB, %
CAD not on BB, %
Calcium blocker Long-acting nitrate
66
38
81
57
*Abbreviations: CAD, coronary artery disease; BB, beta blocker. BetaBlockers and 8ensitivity of Treadmill Test(Martin, Henkin, Seadon)
probably not feasible because of cost considerations. Since our study is not randomized, there is potential for selection bias from some unrecognized factor other than beta blockers to account for the difference in the sensitivity we noted. The more frequent concomitant use of calcium channel blockers and long-acting nitrates in our patients on beta blockers may be responsible for some of the difference in sensitivity we detected. However, Hockings et all investigated the effect of single dose intravenous (IV)propranolol on the results of stress redistribution thallium scans in a small number of patients in a randomized controlled fashion. They utilized an upright treadmill protocol in nine patients, giving a loading dose of IV propranolol in a randomized placebo controlled crossover format. In one of their nine patients, an abnormal stress scan, off propranolol, was completely normal on propranolol. Overall, propranolol tended to decrease both the severity of defects as well as the number of defects, using paired segmental analysis. Pohost et al," in an earlier study, also reported a trend toward a decreased sensitivity of the thallium treadmill test in patients receiving propranolol, particularly in patients whose electrocardiographic response was normal. The concurrence of our data with Hoekings' and Pohosts' reports leads us to suspect that beta blockers may significantly decrease the sensitivity of the thallium treadmill test for some patients. Propranolol has also been shown to significantly decrease the specificity (87 vs 42 percent) of thallium scans done in conjunction with supine bicycle stress. 3 Treadmill tests, including thallium treadmill tests, are frequently used to assess the severity of coronary artery disease. Clinicians often try to select (noninvasively) higher risk patients with three-vessel disease or left main coronary artery disease by looking for early or markedly positive ECG responses to exercise. Beta blockers have recently been reported to decrease the predictive value of the ECG response to exercise in this setting." Calcium channel blockers and even longacting nitrates may also impair the ability of the treadmill to select patients likely to have extensive coronary artery disease. S A completely unanswered issue is whether the patient whose treadmill test result becomes less abnormal on drug therapy also improves his prognosis, independent of the severity of his underlying coronary anatomy.
There is evidence that the underestimation of the extent of disease based on thallium scans in patients taking propranolol may be related to more than just its effect on heart rate. I However, if one uses blunting of heart rate response to exercise as a sign of beta blocker activity, one would estimate that propranolol should be withheld a minimum of 14 hours prior to a diagnostic thallium treadmill test. This is based on data from Shiroff et al" who have shown that normal volunteers will reach 86 percent of their maximal heart rate response 14 hours after propranolol withdrawal. Since other prolonged cardiac effects of propranolol may be present in addition to its effect on heart rate, consideration should be given to an even longer period of withdrawal if possible. A reasonable period is 24 hours for propranolol, but several days may be necessary for longer acting preparations such as metoprolol or atenolol. Generally, patients stable enough to have a symptom-limited exercise stress test should be able to tolerate a short period of beta blocker withdrawal, especially if given careful instructions to report any change in their anginal pattern and instructed in the use of short acting sublingual nitroglycerin. Given the expense of the thallium treadmill test and the need to utilize resources wisely, we feel physicians should fully appreciate the higher false negative rate for patients receiving beta blockers (24 vs 10 percent), and consider withholding them as well as other long acting drugs prior to diagnostic studies. REFERENCES 1 Hockings B, Saltissi S, Croft DN, Webb-Peploe MM. Effect of beta adrenergic blockade on thallium-201 myocardial perfusion imaging. Br Heart J 1983; 49:83-89. 2 Pohost GM, Alpert NM, Ingwall JS, Strauss HW. Thallium redistribution: mechanisms and clinical utility. Semin Nucl Med 1980; 10:70-93 3 Osbakken MD, Okada RD, Boucher CA, Strauss HW, Pohost GM. Comparison of exercise perfusion and ventricular function imaging: an analysis of factors affecting the diagnostic accuracy of each technique. JACC 1984; 3:272-83 4 Ho SW-C, McCamish MJ, 'Iaylor RR. Effect of beta-adrenergic blockade on the results of exercise testing related to the extent of coronary artery disease. Am J Cardiol 1985; 55:258-62 5 Mukharji J, Kremers M, Lipscomb K, Blomqvist CG. Early positive exercise test and extensive coronary disease: effect of antianginal therapy. Am J Cardioll985;55:267-70 6 Shiroff RA, Levenson L~ Zelis R, Shiroff JE, Schneck DW, Hayes AH Jr. Duration of action of propranolol on heart rate during exercise stress testing.Cardiovasc Medl978;3:1029-32
CHEST I 92 131 SEPTEMBER, 1987
487
The effect beta blockers (BB)may have on the sensitivity of the thallium treadmill test (Th-TMT) is controversial. The purpose of this study was to test the hypothesis that BB decrease the sensitivity of the Th-TMT. 1\vo hundred three patients over a two-year periodwere identi6ed who satis6ed the following criteria. All had symptom-limited upright treadmill exercise tests with stress and redistribution thallium imaging, as well as coronary angiography within two months of the Th-TMT. or58 patients with CAD not on
BB, 52 had an abnormal Th-TMT scan (sensitivity 90 percent), In comparison, the sensitivity of the 'Ih- TMT scan in the 88 patients with CAD receiving BB was 76 percent (p
Thallium treadmill tests are frequently done to diagnose the presence and severity of coronary artery disease. Patients are often sent for this relatively expensive test while taking beta blockers without thought to what influence these drugs may have on the diagnostic utility of the test. In an effort to address this question, we reviewed the sensitivity of stress/redistribution thallium scans in 203 patients. Of these patients, 55 percent were on beta blockers at the time of their thallium treadmill test.
treadmill scan (sensitivity 90 percent). In comparison, the sensitivity of the thallium treadmill test scan in the 88 patients with coronary artery disease receiving beta blockers was 76 percent (p
METHODS
Over a two-year period, 203 patients were identi6ed at our medical center who satisfied the following criteria: (1) all had symptom limited upright treadmill exercise tests with stress and redistribution thallium imaging. (2) All patients also had coronary angiography within two months of the thallium treadmill test. Patients with any significant intervening clinical event, as well as any patient status post coronary artery bypass surgery were excluded. Coronary artery disease was defined as greater than or equal to 70 percent luminal diameter narrowing in one or more major arterial branches. In addition, detailed information was available for the last 122 consecutive patients, including severity of coronary artery disease, as well as use of concomitant drugs such as calcium channel blockers and long-acting nitrates. The chi-square test was used when comparing the sensitivity of the stress/rest thallium scan for diagnosing coronary artery disease as well as when assessing use of concomitant drugs. RESULTS
Of 58 patients with coronary artery disease not receiving beta blockers, 52 had an abnormal thallium *From the Department of Medicine, Northwestern University Medical School, Chicago, and the Departments of Medicine and Radiology, Loyola University Medical Center, Maywood, Illinois. tAssistant Professor of Medicine. *Professor of Radiology. 'Professor of Medicine. Manuscript received September 11; revision accepted March 23.
v.
DISCUSSION
A large randomized study evaluating the effects of beta blockers on the sensitivity of thallium scans is Table I-Severity ojCorontJ'l/ Artery DiBeaae* Severity of CAD
CADonBB, %
1 Vessel disease 2 Vessel disease 3 Vessel disease
32 39
Left main
CAD not on BB, % 25 33 36
24
6
5
*Abbreviations: CAD, coronary artery disease; BB, beta blocker.
Table 2-Concomitant Drug Therapy* Concomitant Drug
CAD on BB, %
CAD not on BB, %
Calcium blocker Long-acting nitrate
66
38
81
57
*Abbreviations: CAD, coronary artery disease; BB, beta blocker. BetaBlockers and 8ensitivity of Treadmill Test(Martin, Henkin, Seadon)
probably not feasible because of cost considerations. Since our study is not randomized, there is potential for selection bias from some unrecognized factor other than beta blockers to account for the difference in the sensitivity we noted. The more frequent concomitant use of calcium channel blockers and long-acting nitrates in our patients on beta blockers may be responsible for some of the difference in sensitivity we detected. However, Hockings et all investigated the effect of single dose intravenous (IV)propranolol on the results of stress redistribution thallium scans in a small number of patients in a randomized controlled fashion. They utilized an upright treadmill protocol in nine patients, giving a loading dose of IV propranolol in a randomized placebo controlled crossover format. In one of their nine patients, an abnormal stress scan, off propranolol, was completely normal on propranolol. Overall, propranolol tended to decrease both the severity of defects as well as the number of defects, using paired segmental analysis. Pohost et al," in an earlier study, also reported a trend toward a decreased sensitivity of the thallium treadmill test in patients receiving propranolol, particularly in patients whose electrocardiographic response was normal. The concurrence of our data with Hoekings' and Pohosts' reports leads us to suspect that beta blockers may significantly decrease the sensitivity of the thallium treadmill test for some patients. Propranolol has also been shown to significantly decrease the specificity (87 vs 42 percent) of thallium scans done in conjunction with supine bicycle stress. 3 Treadmill tests, including thallium treadmill tests, are frequently used to assess the severity of coronary artery disease. Clinicians often try to select (noninvasively) higher risk patients with three-vessel disease or left main coronary artery disease by looking for early or markedly positive ECG responses to exercise. Beta blockers have recently been reported to decrease the predictive value of the ECG response to exercise in this setting." Calcium channel blockers and even longacting nitrates may also impair the ability of the treadmill to select patients likely to have extensive coronary artery disease. S A completely unanswered issue is whether the patient whose treadmill test result becomes less abnormal on drug therapy also improves his prognosis, independent of the severity of his underlying coronary anatomy.
There is evidence that the underestimation of the extent of disease based on thallium scans in patients taking propranolol may be related to more than just its effect on heart rate. I However, if one uses blunting of heart rate response to exercise as a sign of beta blocker activity, one would estimate that propranolol should be withheld a minimum of 14 hours prior to a diagnostic thallium treadmill test. This is based on data from Shiroff et al" who have shown that normal volunteers will reach 86 percent of their maximal heart rate response 14 hours after propranolol withdrawal. Since other prolonged cardiac effects of propranolol may be present in addition to its effect on heart rate, consideration should be given to an even longer period of withdrawal if possible. A reasonable period is 24 hours for propranolol, but several days may be necessary for longer acting preparations such as metoprolol or atenolol. Generally, patients stable enough to have a symptom-limited exercise stress test should be able to tolerate a short period of beta blocker withdrawal, especially if given careful instructions to report any change in their anginal pattern and instructed in the use of short acting sublingual nitroglycerin. Given the expense of the thallium treadmill test and the need to utilize resources wisely, we feel physicians should fully appreciate the higher false negative rate for patients receiving beta blockers (24 vs 10 percent), and consider withholding them as well as other long acting drugs prior to diagnostic studies. REFERENCES 1 Hockings B, Saltissi S, Croft DN, Webb-Peploe MM. Effect of beta adrenergic blockade on thallium-201 myocardial perfusion imaging. Br Heart J 1983; 49:83-89. 2 Pohost GM, Alpert NM, Ingwall JS, Strauss HW. Thallium redistribution: mechanisms and clinical utility. Semin Nucl Med 1980; 10:70-93 3 Osbakken MD, Okada RD, Boucher CA, Strauss HW, Pohost GM. Comparison of exercise perfusion and ventricular function imaging: an analysis of factors affecting the diagnostic accuracy of each technique. JACC 1984; 3:272-83 4 Ho SW-C, McCamish MJ, 'Iaylor RR. Effect of beta-adrenergic blockade on the results of exercise testing related to the extent of coronary artery disease. Am J Cardiol 1985; 55:258-62 5 Mukharji J, Kremers M, Lipscomb K, Blomqvist CG. Early positive exercise test and extensive coronary disease: effect of antianginal therapy. Am J Cardioll985;55:267-70 6 Shiroff RA, Levenson L~ Zelis R, Shiroff JE, Schneck DW, Hayes AH Jr. Duration of action of propranolol on heart rate during exercise stress testing.Cardiovasc Medl978;3:1029-32
CHEST I 92 131 SEPTEMBER, 1987
487