Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Stress testing: The effect of medications and methylxanthines

Panithaya Chareonthaitawee, MD
J. Wells Askew, MD
Section Editors
Gary V Heller, MD, PhD, FACC, MASNC
Patricia A Pellikka, MD, FACC, FAHA, FASE
Deputy Editor
Brian C Downey, MD, FACC


For the majority of patients undergoing a stress test, the primary goal is to identify myocardial ischemia due to coronary heart disease (CHD). Depending on the stress test modality, ischemia may manifest in the form of symptoms, hemodynamic findings, electrocardiographic abnormalities, stress-induced perfusion defects, or regional wall motion abnormalities.

In patients with known or suspected CHD, the presence and extent of ischemia on stress testing are used to guide medical therapy and/or determine the need for further diagnostic and therapeutic procedures. Thus, factors that impact the sensitivity and specificity of stress testing for the detection of ischemia may lead to either patients not receiving appropriate therapy or to unnecessary procedures and treatment with their attendant risks and costs, respectively. Many factors (eg, pre-existing electrocardiographic abnormalities, sex, body habitus, etc) can affect a stress test’s ability to accurately identify myocardial ischemia.

The interaction between major cardiovascular medications, dietary factors (namely items containing caffeine), and stress testing and our recommendations for continuing or discontinuing the individual drug or dietary component will be discussed here. Indications and procedures for stress testing are discussed separately. (See "Selecting the optimal cardiac stress test" and "Stress testing for the diagnosis of obstructive coronary heart disease" and "Exercise ECG testing: Performing the test and interpreting the ECG results" and "Overview of stress radionuclide myocardial perfusion imaging" and "Overview of stress echocardiography".)


Before discussing the impact of medications and dietary factors on the detection of myocardial ischemia on stress testing, important concepts regarding stress testing for coronary heart disease (CHD) must be considered.

The manifestations of CHD identified following stress with exercise or dobutamine require the ability to increase myocardial oxygen demand by increasing heart rate, blood pressure, and/or left ventricular contractility above a certain threshold to provoke myocardial ischemia. Vasodilator-stress induced manifestations of CHD depend on a hyperemic coronary blood flow differential between normal and abnormal coronary arteries, and are not dependent on increasing heart rate, blood pressure, or contractility. (See "Exercise ECG testing: Performing the test and interpreting the ECG results" and "Overview of stress radionuclide myocardial perfusion imaging" and "Overview of stress echocardiography".)

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Nov 02, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Henzlova MJ, Duvall WL, Einstein AJ, et al. ASNC imaging guidelines for SPECT nuclear cardiology procedures: Stress, protocols, and tracers. J Nucl Cardiol 2016; 23:606.
  2. Tejani FH, Thompson RC, Kristy R, Bukofzer S. Effect of caffeine on SPECT myocardial perfusion imaging during regadenoson pharmacologic stress: a prospective, randomized, multicenter study. Int J Cardiovasc Imaging 2014; 30:979.
  3. Zoghbi GJ, Htay T, Aqel R, et al. Effect of caffeine on ischemia detection by adenosine single-photon emission computed tomography perfusion imaging. J Am Coll Cardiol 2006; 47:2296.
  4. Gaemperli O, Schepis T, Koepfli P, et al. Interaction of caffeine with regadenoson-induced hyperemic myocardial blood flow as measured by positron emission tomography: a randomized, double-blind, placebo-controlled crossover trial. J Am Coll Cardiol 2008; 51:328.
  5. Zoghbi GJ, Dorfman TA, Iskandrian AE. The effects of medications on myocardial perfusion. J Am Coll Cardiol 2008; 52:401.
  6. Gibbons RJ, Balady GJ, Bricker JT, et al. ACC/AHA 2002 guideline update for exercise testing: summary article. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines). J Am Coll Cardiol 2002; 40:1531.
  7. Bortone AS, Hess OM, Gaglione A, et al. Effect of intravenous propranolol on coronary vasomotion at rest and during dynamic exercise in patients with coronary artery disease. Circulation 1990; 81:1225.
  8. Kern MJ, Ganz P, Horowitz JD, et al. Potentiation of coronary vasoconstriction by beta-adrenergic blockade in patients with coronary artery disease. Circulation 1983; 67:1178.
  9. Vatner SF, Hintze TH. Mechanism of constriction of large coronary arteries by beta-adrenergic receptor blockade. Circ Res 1983; 53:389.
  10. Picano E. Dipyridamole-echocardiography test: historical background and physiologic basis. Eur Heart J 1989; 10:365.
  11. Taillefer R, Ahlberg AW, Masood Y, et al. Acute beta-blockade reduces the extent and severity of myocardial perfusion defects with dipyridamole Tc-99m sestamibi SPECT imaging. J Am Coll Cardiol 2003; 42:1475.
  12. Vatner SF, Hintze TH, Macho P. Regulation of large coronary arteries by beta-adrenergic mechanisms in the conscious dog. Circ Res 1982; 51:56.
  13. Hodgson JM, Cohen MD, Szentpetery S, Thames MD. Effects of regional alpha- and beta-blockade on resting and hyperemic coronary blood flow in conscious, unstressed humans. Circulation 1989; 79:797.
  14. Ferro A, Kaumann AJ, Brown MJ. Beta-adrenoceptor subtypes in human coronary artery: desensitization of beta 2-adrenergic vasorelaxation by chronic beta 1-adrenergic stimulation in vitro. J Cardiovasc Pharmacol 1995; 25:134.
  15. RIVER GL, ROBBINS AB, SCHWARTZ SO. S-C hemoglobin: a clinical study. Blood 1961; 18:385.
  16. Chierchia S, Muiesan L, Davies A, et al. Role of the sympathetic nervous system in the pathogenesis of chronic stable angina. Implications for the mechanism of action of beta-blockers. Circulation 1990; 82:II71.
  17. Egstrup K, Andersen PE Jr. Transient myocardial ischemia during nifedipine therapy in stable angina pectoris, and its relation to coronary collateral flow and comparison with metoprolol. Am J Cardiol 1993; 71:177.
  18. Herbert WG, Dubach P, Lehmann KG, Froelicher VF. Effect of beta-blockade on the interpretation of the exercise ECG: ST level versus delta ST/HR index. Am Heart J 1991; 122:993.
  19. Narahara KA, Thompson CJ, Hazen JF, et al. The effect of beta blockade on single photon emission computed tomographic (SPECT) thallium-201 images in patients with coronary disease. Am Heart J 1989; 117:1030.
  20. Martin GJ, Henkin RE, Scanlon PJ. Beta blockers and the sensitivity of the thallium treadmill test. Chest 1987; 92:486.
  21. Fallahi B, Beiki D, Akbarpour S, et al. Withholding or continuing beta-blocker treatment before dipyridamole myocardial perfusion imaging for the diagnosis of coronary artery disease? A randomized clinical trial. Daru 2013; 21:8.
  22. Shehata AR, Gillam LD, Mascitelli VA, et al. Impact of acute propranolol administration on dobutamine-induced myocardial ischemia as evaluated by myocardial perfusion imaging and echocardiography. Am J Cardiol 1997; 80:268.
  23. Camarozano AC, Siqueira-Filho AG, Weitzel LH, et al. The effects of early administration of atropine during dobutamine stress echocardiography: advantages and disadvantages of early dobutamine-atropine protocol. Cardiovasc Ultrasound 2006; 4:17.
  24. Ling LH, Pellikka PA, Mahoney DW, et al. Atropine augmentation in dobutamine stress echocardiography: role and incremental value in a clinical practice setting. J Am Coll Cardiol 1996; 28:551.
  25. Chen L, Ma L, de Prada VA, et al. Effects of beta-blockade and atropine on ischemic responses in left ventricular regions subtending coronary stenosis during dobutamine stress echocardiography. J Am Coll Cardiol 1996; 28:1866.
  26. Follath F. The role of calcium antagonists in the treatment of myocardial ischemia. Am Heart J 1989; 118:1093.
  27. Pepine CJ, Lambert CR. Effects of nicardipine on coronary blood flow. Am Heart J 1988; 116:248.
  28. Chaffman M, Brogden RN. Diltiazem. A review of its pharmacological properties and therapeutic efficacy. Drugs 1985; 29:387.
  29. Moskowitz RM, Piccini PA, Nacarelli GV, Zelis R. Nifedipine therapy for stable angina pectoris: preliminary results of effects on angina frequency and treadmill exercise response. Am J Cardiol 1979; 44:811.
  30. Fox KM, Deanfield J, Jonathan A, Selwyn A. The dose-response effects of nifedipine of ST-segment changes in exercise testing: preliminary studies. Cardiology 1981; 68 Suppl 2:209.
  31. Rice KR, Gervino E, Jarisch WR, Stone PH. Effects of nifedipine on myocardial perfusion during exercise in chronic stable angina pectoris. Am J Cardiol 1990; 65:1097.
  32. Dodi C, Pingitore A, Sicari R, et al. Effects of antianginal therapy with a calcium antagonist and nitrates on dobutamine-atropine stress echocardiography. Comparison with exercise electrocardiography. Eur Heart J 1997; 18:242.
  33. Sharir T, Rabinowitz B, Livschitz S, et al. Underestimation of extent and severity of coronary artery disease by dipyridamole stress thallium-201 single-photon emission computed tomographic myocardial perfusion imaging in patients taking antianginal drugs. J Am Coll Cardiol 1998; 31:1540.
  34. Ellestad M. Stress Testing Principles and Practice, Oxford University Press, Inc, New York 2003.
  35. Hintze TH, Vatner SF. Comparison of effects of nifedipine and nitroglycerin on large and small coronary arteries and cardiac function in conscious dogs. Circ Res 1983; 52:I139.
  36. Nagao T, Murata S, Sato M. Effects of diltiazem (CRD-401) on developed coronary collaterals in the dog. Jpn J Pharmacol 1975; 25:281.
  37. Fallen EL, Nahmias C, Scheffel A, et al. Redistribution of myocardial blood flow with topical nitroglycerin in patients with coronary artery disease. Circulation 1995; 91:1381.
  38. Bortone AS, Hess OM, Eberli FR, et al. Abnormal coronary vasomotion during exercise in patients with normal coronary arteries and reduced coronary flow reserve. Circulation 1989; 79:516.
  39. Wayne VS, Fagan ET, McConachy DL. The Effects of Isosorbide Dinitrate on the Exercise Test. J Cardiopulm Rehabil Prev 1987; 7:239.
  40. Mahmarian JJ, Fenimore NL, Marks GF, et al. Transdermal nitroglycerin patch therapy reduces the extent of exercise-induced myocardial ischemia: results of a double-blind, placebo-controlled trial using quantitative thallium-201 tomography. J Am Coll Cardiol 1994; 24:25.
  41. Tono I, Satoh S, Kanaya T, et al. Alterations in myocardial perfusion during exercise after isosorbide dinitrate infusion in patients with coronary disease: assessment by thallium-201 scintigraphy. Am Heart J 1986; 111:525.
  42. Sudhir K, Chou TM, Hutchison SJ, Chatterjee K. Coronary vasodilation induced by angiotensin-converting enzyme inhibition in vivo: differential contribution of nitric oxide and bradykinin in conductance and resistance arteries. Circulation 1996; 93:1734.
  43. Kitakaze M, Minamino T, Node K, et al. Beneficial effects of inhibition of angiotensin-converting enzyme on ischemic myocardium during coronary hypoperfusion in dogs. Circulation 1995; 92:950.
  44. Ertl G, Kloner RA, Alexander RW, Braunwald E. Limitation of experimental infarct size by an angiotensin-converting enzyme inhibitor. Circulation 1982; 65:40.
  45. Mancini GB, Henry GC, Macaya C, et al. Angiotensin-converting enzyme inhibition with quinapril improves endothelial vasomotor dysfunction in patients with coronary artery disease. The TREND (Trial on Reversing ENdothelial Dysfunction) Study. Circulation 1996; 94:258.
  46. Anderson TJ, Elstein E, Haber H, Charbonneau F. Comparative study of ACE-inhibition, angiotensin II antagonism, and calcium channel blockade on flow-mediated vasodilation in patients with coronary disease (BANFF study). J Am Coll Cardiol 2000; 35:60.
  47. Perondi R, Saino A, Tio RA, et al. ACE inhibition attenuates sympathetic coronary vasoconstriction in patients with coronary artery disease. Circulation 1992; 85:2004.
  48. Kiowski W, Zuber M, Elsasser S, et al. Coronary vasodilatation and improved myocardial lactate metabolism after angiotensin converting enzyme inhibition with cilazapril in patients with congestive heart failure. Am Heart J 1991; 122:1382.
  49. Schneider CA, Voth E, Moka D, et al. Improvement of myocardial blood flow to ischemic regions by angiotensin-converting enzyme inhibition with quinaprilat IV: a study using [15O] water dobutamine stress positron emission tomography. J Am Coll Cardiol 1999; 34:1005.
  50. van den Heuvel AF, Dunselman PH, Kingma T, et al. Reduction of exercise-induced myocardial ischemia during add-on treatment with the angiotensin-converting enzyme inhibitor enalapril in patients with normal left ventricular function and optimal beta blockade. J Am Coll Cardiol 2001; 37:470.
  51. Longobardi G, Ferrara N, Leosco D, et al. Failure of protective effect of captopril and enalapril on exercise and dipyridamole-induced myocardial ischemia. Am J Cardiol 1995; 76:255.
  52. Benndorf RA, Appel D, Maas R, et al. Telmisartan improves endothelial function in patients with essential hypertension. J Cardiovasc Pharmacol 2007; 50:367.
  53. Tomás JP, Moya JL, Barrios V, et al. Effect of candesartan on coronary flow reserve in patients with systemic hypertension. J Hypertens 2006; 24:2109.
  54. Higuchi T, Abletshauser C, Nekolla SG, et al. Effect of the angiotensin receptor blocker Valsartan on coronary microvascular flow reserve in moderately hypertensive patients with stable coronary artery disease. Microcirculation 2007; 14:805.
  55. Thorne S, Mullen MJ, Clarkson P, et al. Early endothelial dysfunction in adults at risk from atherosclerosis: different responses to L-arginine. J Am Coll Cardiol 1998; 32:110.
  56. Egashira K, Hirooka Y, Kuga T, et al. Effects of L-arginine supplementation on endothelium-dependent coronary vasodilation in patients with angina pectoris and normal coronary arteriograms. Circulation 1996; 94:130.
  57. Ceremuzyński L, Chamiec T, Herbaczyńska-Cedro K. Effect of supplemental oral L-arginine on exercise capacity in patients with stable angina pectoris. Am J Cardiol 1997; 80:331.
  58. Indolfi C, Piscione F, Russolillo E, et al. Digoxin-induced vasoconstriction of normal and atherosclerotic epicardial coronary arteries. Am J Cardiol 1991; 68:1274.
  59. Sketch MH, Mooss AN, Butler ML, et al. Digoxin-induced positive exercise tests: their clinical and prognostic significance. Am J Cardiol 1981; 48:655.
  60. LeWinter MM, Crawford MH, O'Rourke RA, Karliner JS. The effects of oral propranolol, digoxin and combination therapy on the resting and exercise electrocardiogram. Am Heart J 1977; 93:202.
  61. Clark PI, Glasser SP, Lyman GH, et al. Relation of results of exercise stress tests in young women to phases of the menstrual cycle. Am J Cardiol 1988; 61:197.
  62. Jaffe MD. Effect of oestrogens on postexercise electrocardiogram. Br Heart J 1976; 38:1299.
  63. Marmor A, Zeira M, Zohar S. Effects of bilateral hystero-salpingo-oophorectomy on exercise-induced ST-segment abnormalities in young women. Am J Cardiol 1993; 71:1118.
  64. Henzlova MJ, Croft LB, Diamond JA. Effect of hormone replacement therapy on the electrocardiographic response to exercise. J Nucl Cardiol 2002; 9:385.
  65. Bird JG, McCully RB, Pellikka PA, Kane GC. Dobutamine Stress Echocardiography: Impact of Abnormal Blood Potassium Levels on Cardiac Arrhythmias. J Am Soc Echocardiogr 2017; 30:595.
  66. Modesto KM, Møller JE, Freeman WK, et al. Safety of exercise stress testing in patients with abnormal concentrations of serum potassium. Am J Cardiol 2006; 97:1247.