Role of nuclear cardiology in evaluating the total ischemic burden in coronary artery disease

  • George A. Beller
    Address for reprints: George A. Beller, MD, Box 158, University of Virginia Medical Center, Charlottesville, Virginia 22908.
    From the Division of Cardiology, Department of Internal Medicine, University of Virginia Medical Center, Charlottesville, Virginia, USA
    Search for articles by this author
      This paper is only available as a PDF. To read, Please Download here.


      Goals of exercise radionuclide imaging are to: (1) enhance sensitivity, specificity and predictive value of coronary artery disease (CAD) detection; (2) noninvasively assess extent and severity of functionally significant CAD; (3) determine prognosis so that specific therapeutic strategies can be more rationally implemented; (4) detect silent ischemia in asymptomatic subjects or in patients with known CAD with a higher degree of specificity than can be accomplished by electrocardiogram stress testing alone; (5) evaluate the response to therapeutic interventions aimed at enhancing coronary blood flow. Two major radionuclide techniques are currently used in evaluating the total ischemic burden in patients with CAD. These are myocardial perfusion imaging with either thallium-201 or rubidium-82, and radionuclide angiography performed after administration of technetium-99m.
      Areas of diminished thallium-201 activity on early postexercise images are abnormal and represent either areas of stress-induced ischemia or myocardial scar. To differentiate between the two, delayed images are obtained to determine if the initial postexercise defect either persists or demonstrates redistribution (i.e., delayed defect disappearance or improvement). Defects demonstrating redistribution represent transient ischemia, whereas areas of previous infarction or scar usually appear as persistent defects. Patients with left main or 3-vessel CAD usually show multiple thallium-201 redistribution defects in more than 1 vascular supply region, a phenomenon often associated with abnormal lung thallium-201 uptake. In terms of radionuclide angiography, the normal ventricular response to exercise has been defined as an absolute increment of at least 5 % in the left ventricular ejection fraction without the development of regional wall motion abnormalities. In response to exercise, patients with multivessel CAD have a more profound decrease in ejection fraction than do patients with less high-risk anatomy. The observation that electrocardiographic and radionuclide markers of ischemia are more common during exercise testing than angina in patients with CAD appears to indicate a significant prevalence of asymptomatic ischemia. Patients who demonstrate thallium-201 redistribution remote from an infarct region, or who have a decrease in left ventricular ejection fraction from rest to exercise during predischarge testing after an uncomplicated myocardial infarction, should be considered for early catheterization. Certain patients demonstrate these abnormal perfusion or functional findings at variable thresholds of double-product response, suggesting that vasoconstriction may sometimes be a component in the ischemic response to stress.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to American Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Beller GA
        Nuclear cardiology: current indications and clinical usefulness.
        Curr Prob Cardiol. 1985; 10: 3-76
        • Pohost GM
        • Zir LM
        • Moore RH
        • McKusick KA
        • Guiney TE
        • Beller GA
        Differentiation of transiently ischemic from infarcted myocardium by serial imaging after a single dose of thallium-201.
        Circulation. 1977; 55: 294-302
        • Gibson RS
        • Watson DD
        • Taylor GJ
        • Crosby IK
        • Wellons HL
        • Holt ND
        • Beller GA
        Prospective assessment of regional myocardial perfusion before and after coronary revascularization surgery by quantitative thallium-201 scintigraphy.
        JACC. 1983; 1: 804-815
        • Diamond GA
        • Forrester JS
        • Hirsch M
        • Staniloff HM
        • Vas R
        • Berman DS
        • Swan HJC
        Application of conditional probability analysis to the clinical diagnosis of coronary artery disease.
        J Clin Invest. 1980; 65: 1210-1221
        • Nygaard TW
        • Gibson RS
        • Ryan JM
        • Gascho JA
        • Watson DD
        • Beller GA
        Prevalence of high-risk thallium-201 scintigraphic findings in left main coronary artery stenosis: comparison with patients with multiple- and singlevessel coronary artery disease.
        Am J Cardiol. 1984; 53: 462-469
        • Pamelia FX
        • Gibson RS
        • Watson DD
        • Craddock GB
        • Sirowatka J
        • Beller GA
        Prognosis with chest pain and normal thallium-201 exercise scintigrams.
        Am J Cardiol. 1985; 55: 920-926
        • Wackers FJTh
        • Russo DJ
        • Russo D
        • Clements JP
        Prognostic significance of normal quantitative planar thallium-201 stress scintigraphy in patients with chest pain.
        JACC. 1985; 6: 27-30
        • Gibson RS
        • Watson DD
        • Craddock GB
        • Crampton RS
        • Kaiser DL
        • Denny MJ
        • Beller GA
        Prediction of cardiac events after uncomplicated myocardial infarction: a prospective study comparing predischarge exercise thallium-201 scintigraphy and coronary angiography.
        Circulation. 1983; 68: 321-336
        • Patterson RE
        • Horowitz SF
        • Eng C
        • Meller J
        • Goldsmith SJ
        • Pichard AD
        • Halgash DA
        • Herman MV
        • Gorlin R
        Can noninvasive exercise test criteria identify patients with left main or 3-vessel coronary disease after a first myocardial infarction?.
        Am J Cardiol. 1983; 51: 361-372
        • Berger BC
        • Watson DD
        • Taylor GJ
        • Craddock GB
        • Martin RP
        • Teates CD
        • Beller GA
        Quantitative thallium-201 exercise scintigraphy for detection of coronary artery disease.
        J Nucl Med. 1981; 22: 585-593
        • McCarthy DM
        • Sciacca RR
        • Blood DK
        • Cannon PJ
        Discriminant function analysis using thallium-201 scintiscans and exercise stress test variables to predict the presence and extent of coronary artery disease.
        Am J Cardiol. 1982; 49: 1917-1926
        • Wackers FJTh
        • Fetterman RC
        • Mattera JA
        • Clements JP
        Quantitative planar thallium-201 stress scintigraphy: a critical evaluation of the method.
        in: Semin Nucl Med. 15. 1985: 46-66
        • Norhara R
        • Kambara H
        • Suzuki Y
        • Tamaki S
        • Kadota K
        • Kawai C
        • Tamaki N
        • Torizuka K
        Stress scintigraphy using single-photon emission computed tomography in the evaluation of coronary artery disease.
        Am J Cardiol. 1984; 53: 1250-1254
        • Ladenheim ML
        • Pollock BH
        • Rozanski A
        • Berman DS
        • Staniloff HM
        • Forrester JS
        • Diamond GA
        Extent and severity of myocardial hypoperfusion as predictors of prognosis in patients with suspected coronary artery disease.
        JACC. 1986; 7: 464-471
        • Brown KA
        • Boucher CA
        • Okada RD
        • Guiney TE
        • Newell JB
        • Strauss HW
        • Pohost GM
        Prognostic value of exercise thallium-201 imaging in patients presenting for evaluation of chest pain.
        JACC. 1983; 1: 994-1001
        • Bateman TM
        • Maddahi J
        • Gray RJ
        • Murphy FL
        • Garcia EV
        • Conklin CM
        • Raymond MJ
        • Stewart ME
        • Swan HJC
        • Berman DS
        Diffuse slow washout of myocardial thallium-201: a new scintigraphic indicator of extensive coronary artery disease.
        JACC. 1984; 4: 55-64
        • Maddahi J
        • Abdulla A
        • Garcia EV
        • Swan HJC
        • Berman DS
        Noninvasive identification of left main and triple vessel coronary artery disease: improved accuracy using quantitative analysis of regional myocardial stress distribution and washout of thallium-201.
        JACC. 1986; 7: 53-60
        • Lilly DR
        • Ryan J
        • Gibson RS
        • Gascho JA
        • Watson DD
        • Kaiser DL
        • Beller GA
        Thallium-201, exercise test and angiographic predictors of cardiac events in patients with chest pain (abstr).
        Circulation. 1985; 72: III-444
        • Smeets JP
        • Rigo P
        • Legrand V
        • Chevigné M
        • Hastir F
        • Kulbertus HE
        Prognostic value of thallium-201 stress myocardial scintigraphy with exercise EGG after myocardial infarction.
        Cardiology. 1981; 68: 67-70
        • Hung J
        • Goris ML
        • Nash E
        • Kraemer HC
        • DeBusk RF
        • Berger III, WE
        • Lew H
        Comparative value of maximal treadmill testing, exercise thallium myocardial perfusion scintigraphy and exercise radionuclide ventriculography for distinguishing high- and low-risk patients soon after acute myocardial infarction.
        Am J Cardiol. 1984; 53: 1221-1227
        • Gibson RS
        • Beller GA
        • Gheorghiade M
        • Nygaard TW
        • Watson DD
        • Huey BL
        • Sayre SL
        • Kaiser DL
        The prevalence and clinical significance of residual myocardial ischemia 2 weeks after uncomplicated non-Q wave infarction: a prospective natural history study.
        Circulation. 1986; 73: 1186-1198
        • Hirzel HO
        • Nuesch K
        • Sialer G
        • Horst W
        • Krayenbuehl HP
        Thallium-201 exercise myocardial imaging to evaluate myocardial perfusion after coronary artery bypass surgery.
        Br Heart J. 1980; 43: 426-435
        • Wijns W
        • Serruys PW
        • Simoons ML
        • van den Brand M
        • de Feijter PJ
        • Reiber JHC
        • Hugenholtz PG
        Predictive value of early maximal exercise test and thallium scintigraphy after successful percutaneous transluminal coronary angioplasty.
        Br Heart J. 1985; 53: 194-200
        • Schuler G
        • Schwarz F
        • Hofmann M
        • Mehmel H
        • Manthey J
        • Mäurer W
        • Rauch B
        • Herrmann H-J
        • Kübler W
        Thrombolysis in acute myocardial infarction using intracoronary streptokinase: assessment by thallium-201 scintigraphy.
        Circulation. 1982; 66: 658-664
        • Fung AY
        • Lai P
        • Juni JE
        • Bourdillon PDV
        • Walton Jr, JA
        • Laufer N
        • Buda AJ
        • Pitt B
        • O'Neill WW
        Prevention of subsequent exercise-induced periinfarct ischemia by emergency coronary angioplasty in acute myocardial infarction: comparison with intracoronary streptokinase.
        JACC. 1986; 8: 496-503
        • Francisco DA
        • Collins SM
        • Go RT
        • Ehrhardt JC
        • Van Kirk OC
        • Marcus ML
        Tomographic thallium-201 myocardial perfusion scintigrams after maximal coronary artery vasodilation with intravenous dipyridamole: comparison of qualitative and quantitative approaches.
        Circulation. 1982; 66: 370-379
        • Adelstein SJ
        • Holman BL
        • Wagner Jr, HN
        • Zaret BL
        Optimal resources for radioactive tracer studies of the heart and circulation: nuclear medicine study group.
        Circulation. 1984; 70: 525A-536A
        • Zaret BL
        • Berger HJ
        Radionuclide studies of ventricular performance in coronary artery disease.
        in: Yu PN Goodwin JF Progress in Cardiology. Lea and Febiger, Philadelphia1983: 33-66
        • Burow RD
        • Strauss HW
        • Singleton R
        • Pond M
        • Rehn T
        • Bailey IK
        • Griffith LC
        • Nickoloff E
        • Pitt B
        Analysis of left ventricular function from multiple gated acquisition cardiac blood pool imaging: comparison to contrast angiography.
        Circulation. 1977; 56: 1024-1028
        • Gibbons RJ
        • Morris KG
        • Lee K
        • Coleman RE
        • Cobb FR
        Assessment of regional left ventricular function using gated radionuclide angiography.
        Am J Cardiol. 1984; 54: 294-300
        • Borer JS
        • Bacharach SL
        • Green MV
        • Kent KM
        • Epstein SE
        • Johnston GS
        Real-time radionuclide cineangiography in the noninvasive evaluation of global and regional left ventricular function at rest and during exercise in patients with coronary-artery disease.
        N Engl J Med. 1977; 296: 839-844
        • Berger HJ
        • Reduto LA
        • Johnstone DE
        • Borkowski H
        • Sands JM
        • Cohen LS
        • Langou RA
        • Gottschalk A
        • Zaret BL
        • Pytlik L
        Global and regional left ventricular response to bicycle exercise in coronary artery disease: assessment by quantitative radionuclide angiocardiography.
        Am J Med. 1979; 66: 13-21
        • Jones RH
        • McEwan P
        • Newman GE
        • Port S
        • Rerych SK
        • Scholz PM
        • Upton MT
        • Peter CA
        • Austin EH
        • Leong K-H
        • Gibbons RJ
        • Cobb FR
        • Coleman RE
        • Sabiston DC
        Accuracy of diagnosis of coronary artery disease by radionuclide measurement of left ventricular function during rest and exercise.
        Circulation. 1981; 64: 586-601
        • Gibbons RJ
        • Lee KL
        • Cobb F
        • Jones RH
        Ejection fraction response to exercise in patients with chest pain and normal coronary arteriograms.
        Circulation. 1981; 64: 952-957
        • Phillips P
        • Borer JS
        • Jacobstein J
        • Plancher K
        • Carter J
        • Moses J
        • Goldstein J
        • Collins M
        • Fisher J
        Prognostically critical coronary stenoses: identification by radionuclide cineangiography (abstr).
        Am J Cardiol. 1982; 49: 991
        • Wallis J
        • Borer JS
        • Moses JW
        • Goldberg H
        • Fisher J
        • Holmes J
        • Goldstein J
        • Rosenfeld I
        Radionuclide cineangiography during exercise: prognostic importance in coronary artery disease (abstr).
        JACC. 1983; 1: 733
        • Cohn PF
        • Brown Jr, EJ
        • Wynne J
        • Holman BL
        • Atkins HL
        Global and regional left ventricular ejection fraction abnormalities during exercise in patients with silent myocardial ischemia.
        JACC. 1983; 1: 931-933
        • Upton MT
        • Rerych SK
        • Newman GE
        • Port S
        • Cobb FR
        • Jones RH
        Detecting abnormalities in left ventricular function during exercise before angina and ST-segment depression.
        Circulation. 1980; 62: 341-349
        • Wasserman AG
        • Katz RJ
        • Cleary P
        • Varma VM
        • Reba RC
        • Ross AM
        Noninvasive detection of multivessel disease after myocardial infarction by exercise radionuclide ventriculography.
        Am J Cardiol. 1982; 50: 1242-1247
        • Morris DD
        • Rozanski A
        • Berman DS
        • Diamond GA
        • Swan HJC
        Noninvasive prediction of the angiographic extent of coronary artery disease after myocardial infarction: comparison of clinical, bicycle exercise electrocardiographic, and ventriculographic parameters.
        Circulation. 1984; 70: 192-201
        • Morris KG
        • Palmeri ST
        • Califf RM
        • McKinnis RA
        • Higginbotham MB
        • Coleman RE
        • Cobb FR
        Value of radionuclide angiography for predicting specific cardiac events after acute myocardial infarction.
        Am J Cardiol. 1985; 55: 318-324
        • Beller GA
        • Gibson RS
        • Watson DD
        Radionuclide methods of identifying patients who may require coronary artery bypass surgery.
        Circulation. 1985; 72: V9-V22
        • DePuey EG
        • Leatherman LL
        • Leachman RD
        • Dear WE
        • Massin EK
        • Mathur VS
        • Burdine JA
        Restenosis after transluminal coronary angioplasty detected with exercise-gated radionuclide ventriculography.
        JACC. 1984; 4: 1103-1113
        • Gould KL
        • Goldstein RA
        • Mullani NA
        • Kirkeeide RL
        • Wong W-H
        • Tewson TJ
        • Berridge MS
        • Bolomey LA
        • Hartz RK
        • Smalling RW
        • Fuentes F
        • Nishikawa A
        Noninvasive assessment of coronary stenoses by myocardial perfusion imaging during pharmacologic coronary vasodilation. VIII. Clinical feasibility of positron cardiac imaging without a cyclotron using generator-produced rubidium-82.
        JACC. 1986; 7: 775-789
        • Selwyn AP
        • Shea M
        • Deanfield JE
        • Wilson R
        • Horlock P
        • O'Brien HA
        Character of transient ischemia in angina pectoris.
        Am J Cardiol. 1986; 58: 21B-25B