Current Cardiology Reports

, 16:465

Assessing Clinical Impact of Myocardial Perfusion Studies: Ischemia or Other Prognostic Indicators?

  • Todd D. Miller
  • John Wells Askew
  • Joerg Herrmann
Nuclear Cardiology (V Dilsizian, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Nuclear Cardiology


One of the major strengths of nuclear myocardial perfusion imaging (MPI) is the robust prognostic databases from observational studies demonstrating significantly different outcomes in patients with low-risk vs high-risk scans. The severity of the MPI defect can be semi-quantitated using the summed stress score (SSS) and summed difference score (SDS). SSS is more strongly associated with mortality, whereas SDS is the better predictor of subsequent coronary angiography and revascularization. The strength of MPI variables as prognostic indicators decreases when adjusted for prognostically important clinical and stress test variables. Nonetheless, most studies of general patient populations have demonstrated that MPI adds incremental prognostic value to clinical and stress test information. In contrast to these positive results from observational studies, the application of MPI ischemia as a treatment guide in several recent trials (DIAD, WOMEN, COURAGE, BARI 2D, STICH) has largely failed to identify patient subsets with improved outcome. This issue will continue to be investigated in the ongoing PROMISE and ISCHEMIA trials.


SPECT (single photon emission computed tomography) MPI (myocardial perfusion imaging) Summed stress score Summed difference score Ischemia Prognosis Coronary artery disease 


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Fihn SD, Gardin JM, Abrams J, et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2012;126:e354–471.PubMedCrossRefGoogle Scholar
  2. 2.
    Nesto RW, Kowalchuk GJ. The ischemic cascade: temporal sequence of hemodynamic, electrocardiographic and symptomatic expressions of ischemia. Am J Cardiol. 1987;59:23C–30.PubMedCrossRefGoogle Scholar
  3. 3.
    Leong-Poi H, Rim S-J, Le DE, Fisher NG, Wei K, Kaul S. Perfusion versus function: the ischemic cascade in demand ischemia: implications of single-vessel versus multivessel stenosis. Circulation. 2002;105:987–92.PubMedCrossRefGoogle Scholar
  4. 4.
    Shaw LJ, Bugiardini R, Merz CNB. Women and ischemic heart disease. Evolving knowledge. J Am Coll Cardiol. 2009;54:1561–75.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Brown KA. Prognostic value of thallium-201 myocardial perfusion imaging. A diagnostic tool comes of age. Circulation. 1991;83:363–81.PubMedCrossRefGoogle Scholar
  6. 6.
    McNeer JF, Margolis JR, Lee KL, et al. The role of the exercise test in the evaluation of patients for ischemic heart disease. Circulation. 1978;57:64–70.PubMedCrossRefGoogle Scholar
  7. 7.
    Yusuf S, Zucker D, Passamani E, et al. Effect of coronary artery bypass graft surgery on survival: overview of 10-year results from randomised trials by the Coronary Artery Bypass Graft Surgery Trialists Collaboration. Lancet. 1994;344:563–70.PubMedCrossRefGoogle Scholar
  8. 8.
    Tricoci P, Allen JM, Kramer JM, Califf RM, Smith SC. Scientific evidence underlying the ACC/AHA Clinical Practice Guidelines. JAMA. 2009;301:831–41.PubMedCrossRefGoogle Scholar
  9. 9.
    Klocke FJ, Baird MG, Bateman TM, et al. ACC/AHA/ASNC Guidelines for the Clinical Use of Cardiac Radionuclide Imaging: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASNC Committee to Revise the 1995 Guidelines for the Clinical Use of Cardiac Radionuclide Imaging) (2003). American College of Cardiology Web Site. Available at: Accessed 19 Sept 2013.
  10. 10.
    Shaw L, Iskandrian A. Prognostic value of gated myocardial perfusion SPECT. J Nucl Cardiol. 2004;11:171–85.PubMedCrossRefGoogle Scholar
  11. 11.•
    Bourque JM, Beller GA. Stress myocardial perfusion imaging for assessing prognosis: an update. JACC: Cardiovasc Imaging. 2011;4:1305–19. This paper is a recent comprehensive review of the prognostic value of stress SPECT.CrossRefGoogle Scholar
  12. 12.
    Di Carli MF, Murthy VL. Cardiac PET/CT for the evaluation of known or suspected coronary artery disease. Radiographics. 2011;31:1239–54.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Hachamovitch R, Nutter B, Hlatky MA, et al. Patient management after noninvasive cardiac imaging: results from SPARC (Study of Myocardial Perfusion and Coronary Anatomy Imaging Roles in Coronary Artery Disease). J Am Coll Cardiol. 2012;59:462–74.PubMedCrossRefGoogle Scholar
  14. 14.•
    Rozanski A, Gransar H, Hayes SW, et al. Temporal trends in the frequency of inducible myocardial ischemia during cardiac stress testing: 1991 to 2009. J Am Coll Cardiol. 2013;61:1054–65. This study highlights the current trend to test lower risk patients with stress imaging.PubMedCrossRefGoogle Scholar
  15. 15.
    Hendel RC, Berman DS, Di Carli MF, et al. ACCF/ASNC/ACR/AHA/ASE/SCCT/SCMR/SNM 2009 Appropriate Use Criteria for Cardiac Radionuclide Imaging: a report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the American Society of Nuclear Cardiology, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the Society of Cardiovascular Computed Tomography, the Society for Cardiovascular Magnetic Resonance, and the Society of Nuclear Medicine endorsed by the American College of Emergency Physicians. J Am Coll Cardiol. 2009;53:2201–29.PubMedCrossRefGoogle Scholar
  16. 16.
    Cerqueira MD, Weissman NJ, Dilsizian V, et al. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: a statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circulation. 2002;105:539–42.PubMedCrossRefGoogle Scholar
  17. 17.
    Ladenheim ML, Pollock BH, Rozanski A, et al. Extent and severity of myocardial hypoperfusion as predictors of prognosis in patients with suspected coronary artery disease. J Am Coll Cardiol. 1986;7:464–71.PubMedCrossRefGoogle Scholar
  18. 18.
    Hachamovitch R, Berman DS, Shaw LJ, et al. Incremental prognostic value of myocardial perfusion single photon emission computed tomography for the prediction of cardiac death: differential stratification for risk of cardiac death and myocardial infarction. Circulation. 1998;97:535–43.PubMedCrossRefGoogle Scholar
  19. 19.
    Sharir T, Germano G, Kang X, et al. Prediction of myocardial infarction versus cardiac death by gated myocardial perfusion SPECT: risk stratification by the amount of stress-induced ischemia and the poststress ejection fraction. J Nucl Med. 2001;42:831–7.PubMedGoogle Scholar
  20. 20.
    Valeti US, Miller TD, Hodge DO, Gibbons RJ. Exercise single-photon emission computed tomography provides effective risk stratification of elderly men and elderly women. Circulation. 2005;111:1771–6.PubMedCrossRefGoogle Scholar
  21. 21.
    Hachamovitch R, Berman DS, Kiat H, et al. Exercise myocardial perfusion SPECT in patients without known coronary artery disease: incremental prognostic value and use in risk stratification. Circulation. 1996;93:905–14.PubMedCrossRefGoogle Scholar
  22. 22.
    Miller TD, Roger VL, Hodge DO, Hopfenspirger MR, Bailey KR, Gibbons RJ. Gender differences and temporal trends in clinical characteristics, stress test results and use of invasive procedures in patients undergoing evaluation for coronary artery disease. J Am Coll Cardiol. 2001;38:690–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Hachamovitch R, Hayes SW, Friedman JD. Comparison of the short-term survival benefit associated with revascularization compared with medical therapy in patients with no prior coronary artery disease undergoing stress myocardial perfusion single photon emission computed tomography. Circulation. 2003;107:2900–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Pryor DB, Shaw L, McCants CB, et al. Value of the history and physical in identifying patients at increased risk for coronary artery disease. Ann Intern Med. 1993;118:81–90.PubMedCrossRefGoogle Scholar
  25. 25.
    Hubbard BL, Gibbons RJ, Lapeyre III AC, Zinsmeister AR, Clements IP. Identification of severe coronary artery disease using simple clinical parameters. Arch Intern Med. 1992;152:309–12.PubMedCrossRefGoogle Scholar
  26. 26.
    Miller TD, Roger VL, Hodge DO, Gibbons RJ. A simple clinical score accurately predicts outcome in a community-based population undergoing stress testing. Am J Med. 2005;118:866–72.PubMedCrossRefGoogle Scholar
  27. 27.
    Kligfield P, Lauer MS. Exercise electrocardiogram testing: beyond the ST segment. Circulation. 2006;114:2070–82.PubMedCrossRefGoogle Scholar
  28. 28.
    Mark DB, Hlatky MA, Harrell JFE, Lee KL, Califf RM, Pryor DB. Exercise treadmill score for predicting prognosis in coronary artery disease. Ann Intern Med. 1987;106:793–800.PubMedCrossRefGoogle Scholar
  29. 29.
    Mark DB, Shaw L, Harrell FE, et al. Prognostic value of a treadmill exercise score in outpatients with suspected coronary artery disease. N Engl J Med. 1991;325:849–53.PubMedCrossRefGoogle Scholar
  30. 30.
    Lauer MS, Pothier CE, Magid DJ, Smith SS, Kattan MW. An externally validated model for predicting long-term survival after exercise treadmill testing in patients with suspected coronary artery disease and a normal electrocardiogram. Ann Intern Med. 2007;147:821–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Snader CE, Marwick TH, Pashkow FJ, Harvey SA, Thomas JD, Lauer MS. Importance of estimated functional capacity as a predictor of all-cause mortality among patients referred for exercise thallium single-photon emission computed tomography: report of 3400 patients from a single center. J Am Coll Cardiol. 1997;30:641–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Pencina MJ, D' Agostino RB, Vasan RS. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med. 2008;27:157–72. discussion 207.PubMedCrossRefGoogle Scholar
  33. 33.
    Shaw LJ, Wilson PWF, Hachamovitch R, Hendel RC, Borges-Neto S, Berman DS. Improved near-term coronary artery disease risk classification with gated stress myocardial perfusion SPECT. JACC: Cardiovasc Imaging. 2010;3:1139–48.CrossRefGoogle Scholar
  34. 34.
    Piccini JP, Starr AZ, Horton JR, et al. Single-photon emission computed tomography myocardial perfusion imaging and the risk of sudden cardiac death in patients with coronary disease and left ventricular ejection fraction >35%. J Am Coll Cardiol. 2010;56:206–14.PubMedCrossRefGoogle Scholar
  35. 35.
    Cerci MSJ, Cerci JJ, Cerci RJ, et al. Myocardial perfusion imaging is a strong predictor of death in women. JACC: Cardiovasc Imaging. 2011;4:880–8.CrossRefGoogle Scholar
  36. 36.
    Candell-Riera J, Ferreira-González I, Marsal JR, et al. Usefulness of exercise test and myocardial perfusion–gated single photon emission computed tomography to improve the prediction of major events. Circ: Cardiovasc Imaging. 2013;6:531–41.Google Scholar
  37. 37.
    Christian TF, Miller TD, Bailey KR, Gibbons RJ. Exercise tomographic Thallium-201 imaging in patients with severe coronary artery disease and normal electrocardiograms. Ann Intern Med. 1994;121:825–32.PubMedCrossRefGoogle Scholar
  38. 38.
    Poornima IG, Miller TD, Christian TF, Hodge DO, Bailey KR, Gibbons RJ. Utility of myocardial perfusion imaging in patients with low-risk treadmill scores. J Am Coll Cardiol. 2004;43:194–9.PubMedCrossRefGoogle Scholar
  39. 39.
    Bourque JM, Holland BH, Watson DD, Beller GA. Achieving an exercise workload of ≥10 metabolic equivalents predicts a very low risk of inducible ischemia: does myocardial perfusion imaging have a role? J Am Coll Cardiol. 2009;54:538–45.PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Bourque J, Charlton G, Holland B, Belyea C, Watson D, Beller G. Prognosis in patients achieving ≥ 10 METS on exercise stress testing: was SPECT imaging useful? J Nucl Cardiol. 2011;18:230–7.PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Kamalesh M, Feigenbaum H, Sawada S. Assessing prognosis in patients with diabetes mellitus—the achilles’ heel of cardiac stress imaging tests? Am J Cardiol. 2007;99:1016–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Klodas E, Miller T, Christian T, Hodge D, Gibbons R. Prognostic significance of ischemic electrocardiographic changes during vasodilator stress testing in patients with normal SPECT images. J Nucl Cardiol. 2003;10:4–8.PubMedCrossRefGoogle Scholar
  43. 43.
    Abbott B, Afshar M, Berger A, Wackers FT. Prognostic significance of ischemic electrocardiographic changes during adenosine infusion in patients with normal myocardial perfusion imaging. J Nucl Cardiol. 2003;10:9–16.PubMedCrossRefGoogle Scholar
  44. 44.
    Gibbons RJ, Hodge DO, Berman DS, et al. Long-term outcome of patients with intermediate-risk exercise electrocardiograms who do not have myocardial perfusion defects on radionuclide imaging. Circulation. 1999;100:2140–5.PubMedCrossRefGoogle Scholar
  45. 45.
    Abidov A, Germano G, Berman D. Transient ischemic dilation ratio: a universal high-risk diagnostic marker in myocardial perfusion imaging. J Nucl Cardiol. 2007;14:497–500.PubMedCrossRefGoogle Scholar
  46. 46.
    Katz JS, Ruisi M, Giedd KN, Rachko M. Assessment of transient ischemic dilation (TID) ratio in gated SPECT myocardial perfusion imaging (MPI) using regadenoson, a new agent for pharmacologic stress testing. J Nucl Cardiol. 2012;19:727–34.PubMedCrossRefGoogle Scholar
  47. 47.
    Berman DS, Kang X, Slomka PJ, et al. Underestimation of extent of ischemia by gated SPECT myocardial perfusion imaging in patients with left main coronary artery disease. J Nucl Cardiol. 2007;14:521–8.PubMedCrossRefGoogle Scholar
  48. 48.
    Sharir T, Germano G, Kavanagh PB, et al. Incremental prognostic value of post-stress left ventricular ejection fraction and volume by gated myocardial perfusion single photon emission computed tomography. Circulation. 1999;100:1035–42.PubMedCrossRefGoogle Scholar
  49. 49.
    Dorbala S, Vangala D, Sampson U, Limaye A, Kwong R, Di Carli MF. Value of vasodilator left ventricular ejection fraction reserve in evaluating the magnitude of myocardium at risk and the extent of angiographic coronary artery disease: a 82Rb PET/CT Study. J Nucl Med. 2007;48:349–58.PubMedGoogle Scholar
  50. 50.
    Wackers FJT, Young LH, Inzucchi SE, et al. Detection of silent myocardial ischemia in asymptomatic diabetic subjects: the DIAD study. Diabetes Care. 2004;27:1954–61.PubMedCrossRefGoogle Scholar
  51. 51.••
    Young LH, Wackers F, Chyun DA, et al. Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes: the DIAD study: a randomized controlled trial. JAMA. 2009;301:1547–55. This report describes the outcome of patients enrolled in the DIAD study, one of the few prospective studies of SPECT imaging. This study found that SPECT imaging could accurately risk stratify this very low risk diabetic population, but the strategy of screening these patients for coronary artery disease using stress SPECT failed to improve outcome in the subset of patients who underwent screening SPECT compared to patients who did not undergo screening.PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.••
    Shaw LJ, Mieres JH, Hendel RH, et al. Comparative effectiveness of exercise electrocardiography with or without myocardial perfusion single photon emission computed tomography in women with suspected coronary artery disease: results from the What Is the Optimal Method for ischemia Evaluation in Women (WOMEN) Trial. Circulation. 2011;124:1239–49. A prospective study that compared stress SPECT to standard exercise treadmill testing in women at intermediate risk for coronary artery disease. Outcome for women who underwent stress SPECT was no better and costs were higher compared to the subset of women who underwent standard exercise treadmill testing.PubMedCrossRefGoogle Scholar
  53. 53.
    Boden WE, O'Rourke RA, Teo KK, et al. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med. 2007;356:1503–16.PubMedCrossRefGoogle Scholar
  54. 54.
    Frye RL, August P, BARI 2D Study Group, et al. A randomized trial of therapies for type 2 diabetes and coronary artery disease. N Engl J Med. 2009;360:2503–15.PubMedCrossRefGoogle Scholar
  55. 55.
    Velazquez EJ, Lee KL, Deja MA, et al. Coronary-artery bypass surgery in patients with left ventricular dysfunction. N Engl J Med. 2011;364:1607–16.PubMedCentralPubMedCrossRefGoogle Scholar
  56. 56.
    Shaw LJ, Berman DS, Maron DJ, et al. Optimal medical therapy with or without percutaneous coronary intervention to reduce ischemic burden: results from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) Trial nuclear substudy. Circulation. 2008;117:1283–91.PubMedCrossRefGoogle Scholar
  57. 57.•
    Shaw LJ, Weintraub WS, Maron DJ, et al. Baseline stress myocardial perfusion imaging results and outcomes in patients with stable ischemic heart disease randomized to optimal medical therapy with or without percutaneous coronary intervention. Am Heart J. 2012;164:243–50. The second COURAGE imaging sub study that found ischemia on SPECT in a general population of patients with angiographic coronary artery disease was not predictive of outcome.PubMedCrossRefGoogle Scholar
  58. 58.•
    Shaw L, Cerqueira M, Brooks M, et al. Impact of left ventricular function and the extent of ischemia and scar by stress myocardial perfusion imaging on prognosis and therapeutic risk reduction in diabetic patients with coronary artery disease: results from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. J Nucl Cardiol. 2012;19:658–69. This imaging sub study from the BARI 2D trial reported that for patients with diabetes ischemia on SPECT was not associated with outcome. There was no interaction between ischemia and treatment assignment to medical therapy alone or revascularization.PubMedCrossRefGoogle Scholar
  59. 59.•
    Panza JA, Holly TA, Asch FM, et al. Inducible myocardial ischemia and outcomes in patients with coronary artery disease and left ventricular dysfunction. J Am Coll Cardiol. 2013;61:1860–70. This imaging sub study from the STICH trial found that for patients with severely reduced left ventricular ejection fraction (less than or equal to 35%) ischemia was not predictive of outcome. There was no interaction between ischemia and treatment assignment to medical therapy alone or coronary artery bypass surgery.PubMedCrossRefGoogle Scholar
  60. 60.
    Bonow RO, Maurer G, Lee KL, et al. Myocardial viability and survival in ischemic left ventricular dysfunction. N Engl J Med. 2011;364:1617–25.PubMedCentralPubMedCrossRefGoogle Scholar
  61. 61.
    National Heart Lung and Blood Institute (NHLBI). PROspective Multicenter Imaging Study for Evaluation of chest pain (PROMISE). Available at: 2013. Accessed 19 Sept 2013.
  62. 62.
    New York University, Vanderbilt University, Albany Stratton VA Medical Center, et al. International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA). Available at: 2013. Accessed 19 Sept 2013.

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Todd D. Miller
    • 1
    • 2
  • John Wells Askew
    • 1
  • Joerg Herrmann
    • 1
  1. 1.Division of Cardiovascular Diseases and the Department of Internal MedicineMayo ClinicRochesterUSA
  2. 2.Mayo ClinicRochesterUSA

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