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and thus much information be obtained ; and, secondly, by. Adenosine drug like ambien dipyridamole , and dobutamine are the most widely available pharmacologic agents for stress testing. Regadenoson, an adenosine analog, has a longer half-life than adenosine, and therefore a bolus versus continuous administration. Adenosine, dipyridamole, and regadenosine are cardiac vasodilators. They dilate coronary vessels, which causes increased blood velocity and flow rate in normal vessels and less of a response in stenotic vessels. This difference in response leads to a steal of flow, and perfusion defects appear in cardiac nuclear scans or as ST-segment changes. Dobutamine is a cardiac inotrope and chronotrope. The heart responds to dobutamine similarly to the way it responds to exercise. This direct coronary artery vasodilation induced by adenosine is attenuated in diseased coronary arteries, which have a reduced coronary flow reserve and cannot further dilate in response to adenosine. This is not the case in healthy or less-diseased coronary arteries in the same patient, which produces relative flow heterogeneity throughout the coronary arteries, resulting in relatively more coronary blood flow in the healthy or less-diseased coronary arteries compared with the more-diseased coronary artery. In most cases, coronary blood flow in the diseased coronary arteries does not decrease. In cases of severe vessel stenosis or total occlusions with compensatory collateral circulation, a decrease in coronary blood flow may occur in the diseased coronary artery, thus inducing ischemia via a coronary steal phenomenon. This regional flow abnormality also induces a perfusion defect during radionuclide imaging. Dipyridamole is an indirect coronary vasodilator that works by increasing intravascular adenosine levels. This occurs by the inhibition of intracellular reuptake and deamination of adenosine. However, the increase in coronary blood flow induced by dipyridamole is less predictable than that of adenosine. In one comparative study of dipyridamole and adenosine, 66% of patients except true coronary steal occurs more frequently. Dobutamine is a synthetic catecholamine, which directly stimulates both beta-1 and beta-2 receptors. A dose-related increase in heart rate, blood pressure, and myocardial contractility occurs. As with physical exertion, dobutamine increases regional myocardial blood flow based on physiological principles of coronary flow reserve. A similar dose-related increase in subepicardial and subendocardial blood flow occurs within vascular beds supplied by significantly stenosed arteries, with most of the increase occurring within the subepicardium rather than the subendocardium. Thus, perfusion abnormalities are induced by the development of regional myocardial ischemia. Regadenoson produces maximal hyperemia quickly and maintains it for an optimal duration that is practical for radionuclide myocardial perfusion imaging. Regadenoson's simple rapid bolus administration and short duration of hyperemic effect point to an advantage of enhanced control for the clinician. Another approach is the use of an imidazole phosphodiesterase inhibitor such as enoximone or milrinone, drugs that are relatively unaffected by concurrent use of a beta-blocker and are used for inotropic support in congestive heart failure. Enoximone stress echocardiography as an additional stress testing modality was evaluated in one study of 45 patients with chronic coronary artery disease and left ventricular dysfunction who underwent echocardiography with both dobutamine and enoximone. Both increased heart rate, but enoximone did not cause a significant change in systolic blood pressure. The positive predictive value and specificity were similar between enoximone and dobutamine. Concordant results were seen in 85% of affected segments, but enoximone had a higher sensitivity in predicting functional recovery after revascularization. Any physical limitation that prevents a patient from exercising maximally is an indication for vasodilator stress testing. Patients taking beta-blockers or other negative chronotropic agents that would inhibit the ability to achieve an adequate heart rate response to exercise are also appropriate candidates for vasodilator stress. Patients with left bundle branch block or ventricular pacemaker should undergo pharmacologic vasodilator stress because exercise stress often produces a false-positive perfusion defect in the interventricular septum. These defects are probably related to decreased septal contractility, which is accompanied by an autoregulated fall in coronary blood flow to the interventricular septum. Exercise stress or any other cause of tachycardia tends to enhance this heterogeneous perfusion by increasing the flow proportionately more in the normally contracting myocardium, resulting in a falsely underperfused interventricular septum on perfusion imaging. Vasodilator stress has been shown to overcome this coronary blood flow autoregulation, resulting in a more homogeneous perfusion pattern. Any physical limitation that prevents a patient from exercising maximally is an indication for vasodilator stress. Patients taking beta-blockers or other negative chronotropic agents that would inhibit the ability to achieve an adequate heart rate response to exercise are also appropriate candidates for vasodilator stress. Patients with left bundle branch block or a ventricular pacemaker should undergo vasodilator stress, because exercise stress often produces a false-positive perfusion defect in the interventricular septum. These defects are probably related to decreased septal contractility, which is accompanied by an autoregulated decrease in coronary blood flow to the interventricular septum. Exercise stress or any other cause of tachycardia tends to enhance this heterogeneous perfusion by increasing the flow proportionately more in the normally contracting myocardium, resulting in a falsely underperfused interventricular septum with perfusion imaging. Vasodilator stress has been shown to overcome this coronary blood flow autoregulation, resulting in a more homogeneous perfusion pattern. Consider dobutamine as a second-line pharmacologic stressor to be used in patients who cannot perform exercise stress and have a contraindication to vasodilator stress. Regadenoson injection is indicated for radionuclide myocardial perfusion imaging in patients unable to undergo adequate exercise stress testing due to body habitus or other comorbidities as outlined in contraindications for exercise stress testing in Medscape Reference article Treadmill Stress Testing. Regadenoson should not be administered to patients with second-degree atrioventricular block or sinus node dysfunction, unless these patients have a functioning artificial pacemaker. Review the patient's medication and caffeine intake. Theophylline can reduce ischemic changes on the ECG with vasodilator stress testing. Calcium channel blockers, beta-blockers, and nitrates can also alter perfusion defects on pharmacologic stress tests and therefore ideally should be withheld for 24 hours prior to pharmacologic stress testing. Instruct patients with diabetes regarding insulin requirements. Stress testing does not successfully identify all high-risk patients. The table below depicts findings and results for stress testing. Blankstein R, Cannon C, Udelson J. Update on pharmacological cardiac stress testing: efficacy, risk stratification and patient selection. Am J Med. 2014 Nov. 127. Patel JJ, Gupta A, Nanda NC. Comparison of hyperemic impedance echocardiography with dobutamine Stress Echocardiography to detect inducible myocardial ischemia: a pilot study. Echocardiography. 2016 Mar. 33 . Shah BR, Cowper PA, O'Brien SM, Jensen N, Patel MR, Douglas PS, et al. Association between physician billing and cardiac stress testing patterns following coronary revascularization. JAMA. 2011 Nov 9. 306. Pazhenkottil AP, Nkoulou RN, Ghadri JR, et al. Prognostic value of cardiac hybrid imaging integrating single-photon emission computed tomography with coronary computed tomography angiography. Eur Heart J. 2011 Jun. 32. Martin WH 3rd, Xian H, Wagner D, Chandiramani P, Bainter E, Ilias-Khan N. Arm exercise as an alternative to pharmacologic stress testing: arm exercise stress testing and outcome. Am Heart J. 2014 Feb. 167. Patel K, Alattar F, Koneru J, Shamoon F. ST-elevation myocardial infarction after pharmacologic persantine stress test in a patient with Wellens' syndrome. Case Rep Emerg Med. 2014. 2014:530451. . FDA Safety Annoucement. FDA warns of rare but serious risk of heart attack and death with cardiac nuclear stress test drugs Lexiscan . Zoghbi GJ, Htay T, Aqel R, Blackmon L, Heo J, Iskandrian AE. Effect of caffeine on ischemia detection by adenosine single-photon emission computed tomography perfusion imaging. J Am Coll Cardiol. 2006 Jun 6. 47. Korosoglou G, Gitsioudis G, Voss A, Lehrke S, Riedle N, Buss SJ, et al. Strain-encoded cardiac magnetic resonance during high-dose dobutamine stress testing for the estimation of cardiac outcomes comparison to clinical parameters and conventional wall motion readings. J Am Coll Cardiol. 2011 Sep 6. 58. Abe S, Takeishi Y, Chiba J, Ikeda K, Tomoike H. Comparison of adenosine and treadmill exercise thallium-201 stress tests for the detection of coronary artery disease. Jpn Circ J. 1993 Dec. 57. Beller GA. New directions in myocardial perfusion imaging. Clin Cardiol. 1993 Feb. 16. Beller GA. Radionuclide perfusion imaging techniques for evaluation of patients with known or suspected coronary artery disease. Adv Intern Med. 1997. 42:139-201. . Botvinick EH. Current methods of pharmacologic stress testing and the potential advantages of new agents. J Nucl Med Technol. 2009 Mar. 37. Cerqueira MD, Nguyen P, Staehr P, Underwood SR, Iskandrian AE. Effects of age, gender, obesity, and diabetes on the efficacy and safety of the selective A2A agonist regadenoson versus adenosine in myocardial perfusion imaging integrated ADVANCE-MPI trial results. JACC Cardiovasc Imaging. 2008 May. 1. Fletcher GF, Flipse TR, Kligfield P, Malouf JR. Current status of ECG stress testing. Curr Probl Cardiol. 1998 Jul. 23. Goraya TY, Jacobsen SJ, Pellikka PA, et al. Prognostic value of treadmill exercise testing in elderly persons. Ann Intern Med. 2000 Jun 6. 132. Guyton AC, Hall JE. Textbook of Medical Physiology. 9th ed. Philadelphia, Pa: 1995. Mansoor MR, Heller GV. Recent developments in the prognostic use of myocardial perfusion imaging. Curr Opin Cardiol. 1997 Nov. 12. Ruf J, Paganelli F, Bonello L, et al. Spare adenosine A2 receptors are associated with positive exercise stress test in coronary artery disease. Mol Med. 2016 Jul 19. 22:. Puente-Maestu L, Palange P, Casaburi R, et al. Use of exercise testing in the evaluation of interventional efficacy: an official ERS statement. Eur Respir J. 2016 Feb. 47 . Sampaio F, Lamata P, Bettencourt N, et al. Assessment of cardiovascular physiology using dobutamine stress cardiovascular magnetic resonance reveals impaired contractile reserve in patients with cirrhotic cardiomyopathy. J Cardiovasc Magn Reson. 2015 Jul 18. 17:61. . Hunter CR, Hill J, Ziadi MC, Beanlands RS, deKemp RA. Biodistribution and radiation dosimetry of . Normal radionuclide uptake . ECGs show a normal sinus rhythm and a sinus rhythm with a left bundle branch block. ECG depicts electrophysiologic events of left bundle branch block. Eric H Yang, MD Associate Professor of Medicine, Director of Cardiac Catherization Laboratory and Interventional Cardiology, Mayo Clinic Arizona Eric H Yang, MD is a member of the following medical societies: Alpha Omega Alpha Disclosure: Nothing to disclose. Justin D Pearlman, MD, ME, PhD, FACC, MA Chief, Division of Cardiology, Director of Cardiology Consultative Service, Director of Cardiology Clinic Service, Director of Cardiology Non-Invasive Laboratory, Chair of Institutional Review Board, University of California, Los Angeles, David Geffen School of Medicine Justin D Pearlman, MD, ME, PhD, FACC, MA is a member of the following medical societies: American College of Cardiology, International Society for Magnetic Resonance in Medicine, American College of Physicians, American Federation for Medical Research, Radiological Society of North America Disclosure: Nothing to disclose. Disclosure: Nothing to disclose..
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