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Differences in Prognostic Value of Myocardial Perfusion Single-Photon Emission Computed Tomography Using High-Efficiency Solid-State Detector Between Men and Women in a Large International Multicenter Study

Originally published Cardiovascular Imaging. 2022;15


    Semiquantitative assessment of stress myocardial perfusion defect has been shown to have greater prognostic value for prediction of major adverse cardiac events (MACE) in women compared with men in single-center studies with conventional single-photon emission computed tomography (SPECT) cameras. We evaluated sex-specific difference in the prognostic value of automated quantification of ischemic total perfusion defect (ITPD) and the interaction between sex and ITPD using high-efficiency SPECT cameras with solid-state detectors in an international multicenter imaging registry (REFINE SPECT [Registry of Fast Myocardial Perfusion Imaging With Next-Generation SPECT]).


    Rest and exercise or pharmacological stress SPECT myocardial perfusion imaging were performed in 17 833 patients from 5 centers. MACE was defined as the first occurrence of death or myocardial infarction. Total perfusion defect (TPD) at rest, stress, and ejection fraction were quantified automatically by software. ITPD was given by stressTPD-restTPD. Cox proportional hazards model was used to evaluate the association between ITPD versus MACE-free survival and expressed as a hazard ratio.


    In 10614 men and 7219 women, with a median follow-up of 4.75 years (interquartile range, 3.7–6.1), there were 1709 MACE. In a multivariable Cox model, after adjusting for revascularization and other confounding variables, ITPD was associated with MACE (hazard ratio, 1.08 [95% CI, 1.05–1.1]; P<0.001). There was an interaction between ITPD and sex (P<0.001); predicted survival for ITPD<5% was worse among men compared to women, whereas survival among women was worse than men for ITPD≥5%, P<0.001.


    In the international, multicenter REFINE SPECT registry, moderate and severe ischemia as quantified by ITPD from high-efficiency SPECT is associated with a worse prognosis in women compared with men.


    *B.K. Tamarappoo and Y. Otaki contributed equally.

    This manuscript was sent to Linda D. Gillam, MD, MPH, Senior Guest Editor, for review by expert referees, editorial decision, and final disposition

    Supplemental Material is available at

    For Sources of Funding and Disclosures, see page 370.

    Correspondence to: Piotr Slomka, PhD, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Ste. Metro 203, Los Angeles, California 90048. Email


    • 1. Wenger NK, Speroff L, Packard B. Cardiovascular health and disease in women.N Engl J Med. 1993; 329:247–256. doi: 10.1056/NEJM199307223290406CrossrefMedlineGoogle Scholar
    • 2. Wenger NK. Coronary heart disease and women: magnitude of the problem.Cardiol Rev. 2002; 10:211–213. doi: 10.1097/00045415-200207000-00005CrossrefMedlineGoogle Scholar
    • 3. Wenger NK. Clinical characteristics of coronary heart disease in women: emphasis on gender differences.Cardiovasc Res. 2002; 53:558–567. doi: 10.1016/s0008-6363(01)00511-9CrossrefMedlineGoogle Scholar
    • 4. Berman DS, Hachamovitch R, Kiat H, Cohen I, Cabico JA, Wang FP, Friedman JD, Germano G, Van Train K, Diamond GA. Incremental value of prognostic testing in patients with known or suspected ischemic heart disease: a basis for optimal utilization of exercise technetium-99m sestamibi myocardial perfusion single-photon emission computed tomography.J Am Coll Cardiol. 1995; 26:639–647. doi: 10.1016/0735-1097(95)00218-SCrossrefMedlineGoogle Scholar
    • 5. Berman DS, Kang X, Van Train KF, Lewin HC, Cohen I, Areeda J, Friedman JD, Germano G, Shaw LJ, Hachamovitch R. Comparative prognostic value of automatic quantitative analysis versus semiquantitative visual analysis of exercise myocardial perfusion single-photon emission computed tomography.J Am Coll Cardiol. 1998; 32:1987–1995. doi: 10.1016/s0735-1097(98)00501-4CrossrefMedlineGoogle Scholar
    • 6. Hachamovitch R, Berman DS, Kiat H, Cohen I, Cabico JA, Friedman J, Diamond GA. Exercise myocardial perfusion SPECT in patients without known coronary artery disease: incremental prognostic value and use in risk stratification.Circulation. 1996; 93:905–914. doi: 10.1161/01.cir.93.5.905LinkGoogle Scholar
    • 7. Berman DS, Hachamovitch R. Risk assessment in patients with stable coronary artery disease: incremental value of nuclear imaging.J Nucl Cardiol. 1996; 3(6 Pt 2):S41–S49. doi: 10.1016/s1071-3581(96)90207-xCrossrefMedlineGoogle Scholar
    • 8. Hachamovitch R, Berman DS, Kiat H, Bairey CN, Cohen I, Cabico A, Friedman J, Germano G, Van Train KF, Diamond GA. Effective risk stratification using exercise myocardial perfusion SPECT in women: gender-related differences in prognostic nuclear testing.J Am Coll Cardiol. 1996; 28:34–44. doi: 10.1016/0735-1097(96)00095-2CrossrefMedlineGoogle Scholar
    • 9. Berman DS, Kang X, Hayes SW, Friedman JD, Cohen I, Abidov A, Shaw LJ, Amanullah AM, Germano G, Hachamovitch R. Adenosine myocardial perfusion single-photon emission computed tomography in women compared with men. Impact of diabetes mellitus on incremental prognostic value and effect on patient management.J Am Coll Cardiol. 2003; 41:1125–1133. doi: 10.1016/s0735-1097(03)00085-8CrossrefMedlineGoogle Scholar
    • 10. Gambhir SS, Berman DS, Ziffer J, Nagler M, Sandler M, Patton J, Hutton B, Sharir T, Haim SB, Haim SB. A novel high-sensitivity rapid-acquisition single-photon cardiac imaging camera.J Nucl Med. 2009; 50:635–643. doi: 10.2967/jnumed.108.060020CrossrefMedlineGoogle Scholar
    • 11. Herzog BA, Buechel RR, Katz R, Brueckner M, Husmann L, Burger IA, Pazhenkottil AP, Valenta I, Gaemperli O, Treyer V, et al.. Nuclear myocardial perfusion imaging with a cadmium-zinc-telluride detector technique: optimized protocol for scan time reduction.J Nucl Med. 2010; 51:46–51. doi: 10.2967/jnumed.109.065532CrossrefMedlineGoogle Scholar
    • 12. Nakazato R, Tamarappoo BK, Kang X, Wolak A, Kite F, Hayes SW, Thomson LE, Friedman JD, Berman DS, Slomka PJ. Quantitative upright-supine high-speed SPECT myocardial perfusion imaging for detection of coronary artery disease: correlation with invasive coronary angiography.J Nucl Med. 2010; 51:1724–1731. doi: 10.2967/jnumed.110.078782CrossrefMedlineGoogle Scholar
    • 13. Arsanjani R, Xu Y, Hayes SW, Fish M, Lemley M, Gerlach J, Dorbala S, Berman DS, Germano G, Slomka P. Comparison of fully automated computer analysis and visual scoring for detection of coronary artery disease from myocardial perfusion SPECT in a large population.J Nucl Med. 2013; 54:221–228. doi: 10.2967/jnumed.112.108969CrossrefMedlineGoogle Scholar
    • 14. Duvall WL, Slomka PJ, Gerlach JR, Sweeny JM, Baber U, Croft LB, Guma KA, George T, Henzlova MJ. High-efficiency SPECT MPI: comparison of automated quantification, visual interpretation, and coronary angiography.J Nucl Cardiol. 2013; 20:763–773. doi: 10.1007/s12350-013-9735-xCrossrefMedlineGoogle Scholar
    • 15. Dakik HA, Hwang WS, Jafar A, Kimball K, Verani MS, Mahmarian JJ. Prognostic value of quantitative stress myocardial perfusion imaging in unstable angina patients with negative cardiac enzymes and no new ischemic ECG changes.J Nucl Cardiol. 2005; 12:32–36. doi: 10.1016/j.nuclcard.2004.10.001CrossrefMedlineGoogle Scholar
    • 16. Leslie WD, Tully SA, Yogendran MS, Ward LM, Nour KA, Metge CJ. Prognostic value of automated quantification of 99mTc-sestamibi myocardial perfusion imaging.J Nucl Med. 2005; 46:204–211.MedlineGoogle Scholar
    • 17. Nakazato R, Berman DS, Gransar H, Hyun M, Miranda-Peats R, Kite FC, Hayes SW, Thomson LE, Friedman JD, Rozanski A, et al.. Prognostic value of quantitative high-speed myocardial perfusion imaging.J Nucl Cardiol. 2012; 19:1113–1123. doi: 10.1007/s12350-012-9619-5CrossrefMedlineGoogle Scholar
    • 18. Otaki Y, Betancur J, Sharir T, Hu LH, Gransar H, Liang JX, Azadani PN, Einstein AJ, Fish MB, Ruddy TD, et al.. 5-Year prognostic value of quantitative versus visual mpi in subtle perfusion defects: results from REFINE SPECT.JACC Cardiovasc Imaging. 2020; 13:774–785. doi: 10.1016/j.jcmg.2019.02.028CrossrefMedlineGoogle Scholar
    • 19. Slomka PJ, Betancur J, Liang JX, Otaki Y, Hu LH, Sharir T, Dorbala S, Di Carli M, Fish MB, Ruddy TD, et al.. Rationale and design of the registry of fast myocardial perfusion imaging with NExt generation SPECT (REFINE SPECT).J Nucl Cardiol. 2020; 27:1010–1021. doi: 10.1007/s12350-018-1326-4CrossrefMedlineGoogle Scholar
    • 20. Dorbala S, Ananthasubramaniam K, Armstrong IS, Chareonthaitawee P, DePuey EG, Einstein AJ, Gropler RJ, Holly TA, Mahmarian JJ, Park MA, et al.. Single Photon Emission Computed Tomography (SPECT) myocardial perfusion imaging guidelines: instrumentation, acquisition, processing, and interpretation.J Nucl Cardiol. 2018; 25:1784–1846. doi: 10.1007/s12350-018-1283-yCrossrefMedlineGoogle Scholar
    • 21. Slomka PJ, Nishina H, Berman DS, Akincioglu C, Abidov A, Friedman JD, Hayes SW, Germano G. Automated quantification of myocardial perfusion SPECT using simplified normal limits.J Nucl Cardiol. 2005; 12:66–77. doi: 10.1016/j.nuclcard.2004.10.006CrossrefMedlineGoogle Scholar
    • 22. DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach.Biometrics. 1988;44:837–845Google Scholar
    • 23. Kim DH, DeLong DM, Clarke-Pearson DM. Restricted mean survival time as a measure to interpret clinical trial results.JAMA Cardiol. 2017; 2:1179–1180. doi: 10.1001/jamacardio.2017.2922CrossrefMedlineGoogle Scholar
    • 24. Metz LD, Beattie M, Hom R, Redberg RF, Grady D, Fleischmann KE. The prognostic value of normal exercise myocardial perfusion imaging and exercise echocardiography: a meta-analysis.J Am Coll Cardiol. 2007; 49:227–237. doi: 10.1016/j.jacc.2006.08.048CrossrefMedlineGoogle Scholar
    • 25. Chang SM, Nabi F, Xu J, Raza U, Mahmarian JJ. Normal stress-only versus standard stress/rest myocardial perfusion imaging: similar patient mortality with reduced radiation exposure.J Am Coll Cardiol. 2010; 55:221–230. doi: 10.1016/j.jacc.2009.09.022CrossrefMedlineGoogle Scholar
    • 26. Cerci MS, Cerci JJ, Cerci RJ, Pereira Neto CC, Trindade E, Delbeke D, da Cunha CL, Vitola JV. Myocardial perfusion imaging is a strong predictor of death in women.JACC Cardiovasc Imaging. 2011; 4:880–888. doi: 10.1016/j.jcmg.2011.06.009CrossrefMedlineGoogle Scholar
    • 27. Kay J, Dorbala S, Goyal A, Fazel R, Di Carli MF, Einstein AJ, Beanlands RS, Merhige ME, Williams BA, Veledar E, et al.. Influence of sex on risk stratification with stress myocardial perfusion Rb-82 positron emission tomography: Results from the PET (Positron Emission Tomography) Prognosis Multicenter Registry.J Am Coll Cardiol. 2013; 62:1866–1876. doi: 10.1016/j.jacc.2013.06.017CrossrefMedlineGoogle Scholar
    • 28. Shaw LJ, Min JK, Nasir K, Xie JX, Berman DS, Miedema MD, Whelton SP, Dardari ZA, Rozanski A, Rumberger J, et al.. Sex differences in calcified plaque and long-term cardiovascular mortality: observations from the CAC Consortium.Eur Heart J. 2018; 39:3727–3735. doi: 10.1093/eurheartj/ehy534CrossrefMedlineGoogle Scholar
    • 29. Xie JX, Eshtehardi P, Varghese T, Goyal A, Mehta PK, Kang W, Leipsic J, Ó Hartaigh B, Bairey Merz CN, Berman DS, et al.. Prognostic significance of nonobstructive left main coronary artery disease in women versus men: long-term outcomes from the CONFIRM (Coronary CT Angiography Evaluation For Clinical Outcomes: An International Multicenter) Registry.Circ Cardiovasc Imaging. 2017; 10:e006246. doi: 10.1161/CIRCIMAGING.117.006246LinkGoogle Scholar
    • 30. Taqueti VR, Shaw LJ, Cook NR, Murthy VL, Shah NR, Foster CR, Hainer J, Blankstein R, Dorbala S, Di Carli MF. Excess cardiovascular risk in women relative to men referred for coronary angiography is associated with severely impaired coronary flow reserve, not obstructive disease.Circulation. 2017; 135:566–577. doi: 10.1161/CIRCULATIONAHA.116.023266LinkGoogle Scholar
    • 31. Murthy VL, Naya M, Taqueti VR, Foster CR, Gaber M, Hainer J, Dorbala S, Blankstein R, Rimoldi O, Camici PG, et al.. Effects of sex on coronary microvascular dysfunction and cardiac outcomes.Circulation. 2014; 129:2518–2527. doi: 10.1161/CIRCULATIONAHA.113.008507LinkGoogle Scholar
    • 32. Ficaro EP, Lee BC, Kritzman JN, Corbett JR. Corridor4DM: the Michigan method for quantitative nuclear cardiology.J Nucl Cardiol. 2007; 14:455–465. doi: 10.1016/j.nuclcard.2007.06.006CrossrefMedlineGoogle Scholar
    • 33. Garcia EV, Faber TL, Cooke CD, Folks RD, Chen J, Santana C. The increasing role of quantification in clinical nuclear cardiology: the Emory approach.J Nucl Cardiol. 2007; 14:420–432. doi: 10.1016/j.nuclcard.2007.06.009CrossrefMedlineGoogle Scholar