Factors affecting sensitivity and specificity of a diagnostic test: the exercise thallium scintigram

      This paper is only available as a PDF. To read, Please Download here.


      Technical and methodological factors might affect the reported accuracies of diagnostic tests. To assess their influence on the accuracy of exercise thallium scintigraphy, the medical literature (1977 to 1986) was non-selectively searched and meta-analysis was applied to the 56 publications thus retrieved. These were analyzed for year of publication, sex and mean age of patients, percentage of patients with angina pectoris, percentage of patients with prior myocardial infarction, percentage of patients taking beta-blocking medications, and for angio-graphic referral (workup) bias, blinding of tests, and technical factors. The percentage of patients with myocardial infarction had the highest correlation with sensitivity (0.45, p = 0.0007). Only the inclusion of subjects with prior infarction and the percentage of men in the study group were independently and significantly (p <0.05) related to test sensitivity. Both the presence of workup bias and publication year adversely affected specificity (p <0.05). Of these two factors, publication year had the strongest association by stepwise linear regression. This analysis suggests that the reported sensitivity of thallium scintigraphy is higher and the specificity lower than that expected in clinical practice because of the presence of workup bias and the inappropriate inclusion of post-infarct patients.
      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 The American Journal of Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Galen RS
        • Gambino SR
        Beyond normality: the predictive value and efficiency of medical diagnoses.
        John Wiley and Sons, New York1975
        • Wulff HR
        • Lennard-Jones JE
        Rational diagnosis and treatment.
        in: An introduction to clinical decision-making. Blackwell Scientific Publications, Oxford1981
        • Griner PF
        • Mayewski RJ
        • Mushlin AI
        • Greenland P
        Selection and interpretation of diagnostic tests and procedures.
        Ann Intern Med. 1981; 94 (4 part 2): 553-592
        • Sox HC
        Probability theory in the use of diagnostic tests.
        in: An introduction to critical study of the literature. 9th ed. Ann Intern Med. 104. 1986: 60-66
        • Ransohoff DF
        • Feinstein AR
        Problems of spectrum and bias in evaluating the efficacy of diagnostic tests.
        N Engl J Med. 1978; 299: 926-930
        • Philbrick JT
        • Horwitz RI
        • Feinstein AR
        Methodologic problems of exercise testing for coronary artery disease: groups, analysis and bias.
        Am J Cardiol. 1980; 46: 807-812
        • Philbrick JT
        • Horwitz RI
        • Feinstein AR
        • Langou RA
        • Chandler JP
        The limited spectrum of patients studied in exercise test research.
        in: Analyzing the tip of the iceberg. 9th ed. JAMA. 248. 1982: 2467-2470
        • Wasson JH
        • Sox HC
        • Neff RK
        • Goldman L
        Clinical prediction rules.
        in: Applications and methodological standards. 9th ed. N Engl J Med. 313. 1985: 793-799
        • Detrano R
        • Leatherman J
        • Salcedo EE
        • Yiannikas J
        • Williams G
        Bayesian analysis versus discriminant function analysis: their relative utility in the diagnosis of coronary disease.
        Circulation. 1986; 73: 970-977
        • Hlatky MA
        • Pryor DB
        • Harrell FE
        • Califf RM
        • Mark DB
        • Rosati RA
        Factors affecting sensitivity and specificity of exercise electrocardiography.
        Am J Med. 1984; 77: 64-71
        • Diamond GA
        • Rozanski A
        • Forrester JS
        • et al.
        A model for assessing the sensitivity and specificity of test subject to selection bias.
        in: Application to exercise radionuclide ventriculography for diagnosis of coronary artery disease. 9th ed. J Chronic Dis. 39. 1986: 343-355
        • Okada RD
        • Boucher CA
        • Strauss HW
        • Pohost GM
        Exercise radionuclide imaging approaches to coronary artery disease.
        Am J Cardiol. 1980; 46: 1188-1204
        • Glass GV
        • McGaw B
        • Smith ML
        Meta-analysis in social research.
        Sage Publications, Beverly Hills1981
        • Sacks HS
        • Berrier J
        • Reitman D
        • Ancona-Berk VA
        • Chalmers TC
        Meta-analysis of randomized controlled trials.
        N Engl J Med. 1987; 316: 450-455
        • Tran ZV
        • Weltman A
        Differential effects of exercise on serum lipid and lipoprotein levels seen with changes in body weight.
        in: A meta-analysis. 9th ed. JAMA. 254. 1985: 919-924
        • Amor M
        • Verdaguer M
        • Karcher G
        • et al.
        Les examens isotopiques a l'effort dans l'isuffisance coronaire.
        Arch Mal Coeur. 1985; 78: 55-64
        • Bailey IK
        • Griffith SC
        • Rouleau J
        • Strauss HW
        • Pitt B
        Thallium-201 myocardial perfusion imaging at rest and during exercise.
        in: Comparative sensitivity to electrocardiography in coronary artery disease. 9th ed. Circulation. 55. 1977: 79-87
        • Berger BC
        • Watson DD
        • Taylor GJ
        • et al.
        Quantitative thallium-201 exercise scintigraphy for detection of coronary artery disease.
        J Nucl Med. 1981; 22: 585-593
        • Blood DK
        • McCarthy DM
        • Sciacca RR
        • Cannon PJ
        Comparison of single-dose and double-dose thallium-201 myocardial perfusion scintigraphy for the detection of coronary artery disease and prior myocardial infarction.
        Circulation. 1978; 58: 777-788
        • Bodenheimer MB
        • Banka VS
        • Fooshee CM
        • Helfant RH
        Extent and severity of coronary heart disease.
        in: Determinations by thallous chloride T1 201 myocardial perfusion scanning and comparison with stress electrocardiography. 9th ed. Arch Intern Med. 139. 1979: 630-634
        • Botvinick EH
        • Taradash MR
        • Shames DM
        • Parmley WW
        Thallium-201 myocardial perfusion scintigraphy for the clinical clarification of normal, abnormal and equivocal electrocardiographic stress tests.
        Am J Cardiol. 1978; 41: 43-51
        • Boucher CA
        • Zir LM
        • Belier GA
        • et al.
        Increased lung uptake of thallium-201 during exercise myocardial imaging: clinical hemodynamic and angiographic implications in patients with coronary artery disease.
        Am J Cardiol. 1980; 46: 189-196
        • Brown KA
        • Boucher CA
        • Okada RD
        • et al.
        Prognostic value of exercise thallium-201 imaging in patients presenting for evaluation of chest pain.
        J Am Coll Cardiol. 1983; 1: 994-1001
        • Burke JF
        • Morganroth J
        • Soffer J
        • Panidis I
        • Chen CC
        • David D
        The cardiokymography exercise test compared to the thallium-201 perfusion exercise test in the diagnosis of coronary artery disease.
        Am Heart J. 1984; 107: 718-725
        • Caldwell JH
        • Hamilton GW
        • Sorenson SG
        • Ritchie JL
        • Williams DL
        • Kennedy JW
        The detection of coronary artery disease with radionuclide techniques: a comparison of rest-exercise thallium imaging and ejection fraction response.
        Circulation. 1980; 61: 610-619
        • Canhasi B
        • Dae M
        • Botvinick E
        • et al.
        Interaction of “supplementary” indicators of ischemia and stress electrocardiography in the diagnosis of multivessel coronary disease.
        J Am Coll Cardiol. 1985; 6: 581-588
        • Carrillo AP
        • Marks DS
        • Pickard D
        • Khaja F
        • Goldstein S
        Correlation of exercise thallium-201 myocardial scans with coronary arteriograms and the maximal exercise test.
        Chest. 1978; 73: 321-326
        • Chaitman BR
        • Brevers G
        • Dupras G
        • Lesperance J
        • Bourassa MG
        Diagnostic impact of thallium scintigraphy and cardiac fluoroscopy when the exercise ECG is strongly positive.
        Am Heart J. 1984; 108: 260-265
        • Ilsley C
        • Stockley A
        • Clitsakis D
        • Layton C
        Normal coronary arteriogram.
        in: An avoidable test?9th ed. Br Heart J. 48. 1982: 580-583
        • Cinotti L
        • Meignan M
        • Usdin JP
        • Vasile N
        • Castaigne A
        Diagnostic value of image processing in myocardial scintigraphy.
        J Nucl Med. 1983; 24: 768-774
        • Dash H
        • Massie BM
        • Botvinick EH
        • Brundage BH
        The noninvasive identification of left main and three-vessel coronary artery disease by myocardial stress perfusion scintigraphy and treadmill exercise electrocardiography.
        Circulation. 1979; 60: 276-284
        • Del Rio-Meraza A
        • Villalpando-Gutierrez J
        • Nava-Lopez G
        • Arevila-Ceballos N
        Correlation between exercise electrocardiographic test, myocardial perfusion test with thallium 201 and contrast coronary arteriography in patients with ischemic heart disease.
        Arch Invest Med (Mex). 1985; 16: 175-189
        • Dunn RF
        • Kelly DT
        • Bailey IK
        • Uren R
        • McLaughlin A
        Serial exercise thallium myocardial perfusion scanning and exercise electrocardiography in the diagnosis of coronary artery disease.
        Aust NZ J Med. 1979; 9: 547-553
        • Faris JV
        • Burt RW
        • Graham MC
        • Knoebel SB
        Thallium-201 myocardial scintigraphy; improved sensitivity, specificity and predictive accuracy by application of a statistical image analysis algorithm.
        Am J Cardiol. 1982; 49: 733-742
        • Friedman TD
        • Greene AC
        • Iskandrian AS
        • Hakki A
        • Kane SA
        • Segal BL
        Exercise thallium-201 myocardial scintigraphy in women: correlation with coronary arteriography.
        Am J Cardiol. 1982; 49: 1632-1637
        • Hamilton GW
        • Trobaugh GB
        • Ritchie JL
        • Gould KL
        • DeReben TA
        • Williams DL
        Myocardial imaging with thallium: an analysis of clinical usefulness based on Bayes' theorem.
        Semin Nucl Med. 1978; 8: 358-364
        • Hirzel HO
        • Nuesch K
        • Krayenbuhl HP
        • Sialer G
        • Horst W
        in: Aussagekraft und stellenwert in der Diagnostik der koronaren herzkrankheit. 9th ed. Schweiz Med Wochenschr. 109. 1979: 1641-1644
        • Hung J
        • Chaitman BR
        • Lam J
        • et al.
        Noninvasive diagnostic test for the evaluation of coronary artery disease in women: a multivariate comparison of cardiac fluoroscopy, exercise electrocardiography and exercise thallium myocardial perfusion scintigraphy.
        J Am Coll Cardiol. 1984; 4: 8-16
        • Hung J
        • Chaitman BR
        • Lam J
        • et al.
        A logistic regression analysis of multiple noninvasive tests for the prediction of the presence and extent of coronary artery disease in men.
        Am Heart J. 1985; 110: 460-469
        • Iskandrian AS
        • Mintz GS
        • Croll MN
        • et al.
        Exercise thallium-201 myocardial scintigraphy: advantages and limitations.
        Cardiology. 1980; 65: 136-152
        • Iskandrian AS
        • Segal BL
        • Haaz W
        • Kane S
        Effects of coronary artery narrowing, collaterals, and left ventricular function on the pattern of myocardial perfusion.
        Catheter Cardiovasc Diagn. 1980; 6: 159-172
        • Jengo JA
        • Freeman R
        • Brizendine M
        • Mena I
        Detection of coronary artery disease: comparison of exercise stress radionuclide angiocardiography and thallium stress perfusion scanning.
        Am J Cardiol. 1980; 45: 535-541
        • Kambara H
        • Kawashita K
        • Yoshida A
        • et al.
        Identification of patients with coronary artery disease using a scoring system of coronary risk factors, electrocardiography and myocardial perfusion imaging.
        Jpn Circ J. 1982; 46: 235-244
        • Kaul S
        • Boucher CA
        • Newell JB
        • et al.
        Determination of the quantitative thallium imaging variables that optimize detection of coronary artery disease.
        J Am Coll Cardiol. 1986; 7: 527-537
        • Lenaers A
        • Block P
        • van Thiel E
        • et al.
        Segmental analysis of T1–201 stress myocardial scintigraphy.
        J Nucl Med. 1977; 18: 509-516
        • Massie BM
        • Wisneski J
        • Hollenberg M
        • Gertz EW
        • Henderson S
        Quantitative analysis of seven-pinhole tomographic thallium-201 scintigrams: improved sensitivity and estimation of the extent of coronary involvement by evaluation of radiotracer uptake and clearance.
        J Am Coll Cardiol. 1984; 3: 1178-1186
        • Massie BM
        • Botvinick EH
        • Brundage BH
        Correlation of thallium-201 scintigrams with coronary anatomy: factors affecting region by region sensitivity.
        Am J Cardiol. 1979; 44: 616-622
        • Melin JA
        • Piret LJ
        • Vanbutsele RJM
        • et al.
        Diagnostic value of exercise electrocardiography and thallium myocardial scintigraphy in patients without previous myocardial infarction: a Bayesian approach.
        Circulation. 1981; 63: 1019-1024
        • Melin JA
        • Wuns W
        • Vanbutsele RJ
        • et al.
        Alternative diagnostic strategies for coronary artery disease in women: demonstration of the usefulness and effiency of probability analysis.
        Circulation. 1985; 71: 535-542
        • Murray RG
        • McKillop JH
        • Bessent RG
        • Hutton I
        • Lorimer AR
        • Lawrie TDV
        Bayesian analysis of stress thallium-201 scintigraphy.
        Eur J Nucl Med. 1981; 6: 201-204
        • Nakashima Y
        • Maeda K
        • Minamiji K
        • Toki Y
        • Fukuzaki H
        Clinical evaluation of stress myocardial scintigraphy with thallium-201 in patients with ischemic heart disease.
        Jpn Circ J. 1982; 46: 245-251
        • O'Hara MJ
        • Lahiri A
        • Whittington JR
        • Crawley JCW
        • Raftery EB
        Detection of high risk coronary artery disease by thallium imaging.
        Br Heart J. 1985; 53: 616-623
        • O'Keefe JC
        • Edwards AC
        • Wiseman J
        • Cooper RA
        • Shuter B
        • Donnelly GL
        Comparison of exercise electrocardiography, thallium-201 myocardial imaging and exercise gated blood pool scan in patients with suspected coronary artery disease.
        Aust NZ J Med. 1983; 13: 45-50
        • 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.
        J Am Coll Cardiol. 1984; 3: 272-278
        • Patterson RE
        • Horowitz SF
        • Eng C
        • et al.
        Can exercise electrocardiography and thallium-201 myocardial imaging exclude the diagnosis of coronary artery disease?.
        in: Bayesian analysis of the clinical limits of exclusion and indications for coronary angiography. 9th ed. Am J Cardiol. 49. 1982: 1127-1135
        • Rizi HR
        • Kline RC
        • Thrall JH
        • et al.
        Thallium-201 myocardial scintigraphy: a critical comparison of seven-pinhole tomography and conventional planar imaging.
        J Nucl Med. 1981; 22: 493-499
        • Ritchie JL
        • Zaret BL
        • Strauss HW
        • et al.
        Myocardial imaging with thallium-201: a multicenter study in patients with angina pectoris or acute myocardial infarction.
        Am J Cardiol. 1978; 42: 345-350
        • Rothendler JA
        • Okada RD
        • Wilson RA
        • et al.
        Effect of a delay in commencing imaging on the ability to detect transient thallium defects.
        J Nucl Med. 1985; 26: 880-883
        • Schicha H
        • Rentrop P
        • Facorro L
        • et al.
        Results of quantitative myocardial scintigraphy with thallium-201 at rest and after maximum exercise—critical analysis of predictive value and clinical application.
        Z Kardiol. 1980; 69: 31-42
        • Schneider E
        • Lutolf UM
        • Glanzmann CH
        • Krayenbuhl HP
        • Horst W
        Ein jahr erfahrung mit der 201-thallium—myokardszintigraphie in der beurteilung koronarer durchblutungsstorungen.
        Schweiz Med Wochenschr. 1977; 107: 1577-1580
        • Silber S
        • Fleck E
        • Klein U
        • Rudolph W
        Wertigkeit der thallium-201-belastungsszintigraphie im vergleich zur belastungselektrokardiographie bei patienten mit koronarer herzerkrankung ohne moydardinfarkt.
        Herz. 1979; 4: 359-369
        • Starling MR
        • Dehmer GJ
        • Lancaster JL
        • et al.
        Segmental coronary artery disease: detection by rotating slant-hole collimator tomography and planar thallium 201 myocardial scintigraphy.
        Radiology. 1985; 157: 231-237
        • Tamaki N
        • Yonekura Y
        • Mukai T
        • et al.
        Segmental analysis of stress thallium myocardial emission tomography for localization of coronary artery disease.
        Eur J Nucl Med. 1984; 9: 99-105
        • Turner DA
        • Battle WE
        • Deshmukh H
        • et al.
        The predictive value of myocardial perfusion scintigraphy after stress in patients without previous myocardial infarction.
        J Nucl Med. 1977; 19: 249-255
        • Uhl GS
        • Kay TN
        • Hickman JR
        Computer-enhanced thallium scintigrams in asymptomatic men with abnormal exercise tests.
        Am J Cardiol. 1981; 48: 1037-1043
        • Underwood DA
        • Rincon G
        • Yiannikas J
        • Cook S
        • MacIntyre WJ
        • Go RT
        Clinical usefulness of thallium-201 scintigraphy in the study of coronary artery disease: a comparison of two exercise systems.
        Cleve Clin Q. 1982; 49: 73-78
        • Van Train K
        • Berman DS
        • Garcia EV
        • et al.
        Quantitative analysis of stress thallium-201 myocardial scintigrams: a multicenter trial.
        J Nucl Med. 1986; 27: 17-25
        • Verani MS
        • Marcus ML
        • Razzak MA
        • Ehrhardt JC
        Sensitivity and specificity of thallium-201 perfusion scintigrams under exercise in the diagnosis of coronary artery disease.
        J Nucl Med. 1978; 19: 773-782
        • Vogel RA
        • Kirch DL
        • LeFree MT
        • Rainwater JO
        • Jensen DP
        • Steel PP
        Thallium-201 myocardial perfusion scintigraphy: results of standard and multi-pinhole tomographic techniques.
        Am J Cardiol. 1979; 43: 787-793
        • Weiner DA
        Accuracy of cardiokymography during exercise testing: results of a multicenter study.
        J Am Coll Cardiol. 1985; 6: 502-509
        • Weintraub WS
        • Madiera SW
        • Bodenheimer MM
        • et al.
        Critical analysis of the application of Bayes' theorem to sequential testing in the noninvasive diagnosis of coronary artery disease.
        Am J Cardiol. 1984; 54: 43-49
        • Gerson MC
        Nuclear cardiology in the investigation of chronic coronary artery disease.
        in: Which test and when?9th ed. JAMA. 250. 1983: 2037-2041
        • Diamond GA
        • Forrester JS
        Analysis of probability as an aid to the clinical diagnosis of coronary artery disease.
        N Engl J Med. 1979; 300: 1350-1358
      1. 9th ed. SAS Users Guide: Statistics 1985 Cary. North Carolina, 1982: 433-506
      2. 9th ed. SAS Users Guide: Statistics 1985 Cary. North Carolina, 1982: 763-774
        • Rozanski A
        • Diamond GA
        • Forrester JS
        • Berman D
        • Morris D
        • Swan HJC
        The declining specificity of exercise radionuclide angiography.
        N Engl J Med. 1983; 309: 518-522
        • Rozanski A
        • Diamond GA
        • Forrester JS
        • Berman DS
        • Morris D
        • Swan HJC
        Alternative referent standards for cardiac normality.
        Ann Intern Med. 1984; 101: 164-171
        • Diamond GA
        Monkey business.
        Am J Cardiol. 1986; 57: 471-475