The rate of myocardial perfusion recovery after steroid therapy and its implication for cardiac events in cardiac sarcoidosis and primarily preserved left ventricular ejection fraction

  • Kazuhiro Koyanagawa
  • Masanao NayaEmail author
  • Tadao Aikawa
  • Osamu Manabe
  • Sho Furuya
  • Masato Kuzume
  • Noriko Oyama-Manabe
  • Hiroshi Ohira
  • Ichizo Tsujino
  • Toshihisa Anzai
Original Article



Sarcoidosis is a multisystemic disorder of unknown cause characterized by immune granuloma formation in the involved organs. Few studies have reported on the myocardial perfusion changes by immunosuppression therapy in cardiac sarcoidosis (CS). Additionally, the relationship between myocardial perfusion changes and prognosis is unknown. Therefore, this study aimed to clarify myocardial perfusion recovery after steroid therapy and its prognostic value for major adverse cardiac events (MACE) in patients with CS.

Methods and Results

Thirty-eight consecutive patients with CS {median age, 63 [interquartile range (IQR) 51–68] years; 10 men} underwent both 18F-fluorodeoxyglucose positron emission tomography/computed tomography (CT) and electrocardiography-gated single-photon emission CT (SPECT) pre- and post-steroid therapy. Patients with improved or preserved myocardial perfusion after post-therapy were defined as the recovery group and those with worsened myocardial perfusion as the non-recovery group. Twenty-six patients (68%) were categorized as the recovery group. MACE occurred in eight patients. The Kaplan–Meier curves revealed a significantly higher rate of MACE in the non-recovery group (17.4%/y vs 2.9%/y, P = 0.007).


Myocardial perfusion was recovered by steroid therapy in 61% and preserved in 8% of patients. Myocardial perfusion recovery after steroid therapy was significantly associated with a low incidence of MACE.



Cardiac sarcoidosis


Single-photon emission computed tomography




Positron emission tomography


Computed tomography


Summed rest score




Major adverse cardiac events





Dr. Aikawa is affiliated with the endowed department of Medtronic Japan Co., Ltd. and Win International Co., Ltd. All other authors have no conflicts of interest to disclose.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was waived due to the retrospective study design.

Supplementary material

12350_2019_1916_MOESM1_ESM.docx (15 kb)
Supplementary material 1 (DOCX 14 kb)
12350_2019_1916_MOESM2_ESM.pptx (809 kb)
Supplementary material 1 (PPTX 809 kb)


  1. 1.
    Newman LS, Rose CS, Maier LA. Sarcoidosis. N Engl J Med. 1997;336:1224–34.CrossRefGoogle Scholar
  2. 2.
    Rybicki BA, Major M, Popovich J Jr, Maliarik MJ, Iannuzzi MC. Racial differences in sarcoidosis incidence: A 5-year study in a health maintenance organization. Am J Epidemiol. 1997;145:234–41.CrossRefGoogle Scholar
  3. 3.
    Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl J Med. 2007;357:2153–65.CrossRefGoogle Scholar
  4. 4.
    Ahmadian A, Pawar S, Govender P, Berman J, Ruberg FL, Miller EJ. The response of FDG uptake to immunosuppressive treatment on FDG PET/CT imaging for cardiac sarcoidosis. J Nucl Cardiol. 2017;24:413–24.CrossRefGoogle Scholar
  5. 5.
    Osborne MT, Hulten EA, Singh A, Waller AH, Bittencourt MS, Stewart GC, et al. Reduction in (1)(8)F-fluorodeoxyglucose uptake on serial cardiac positron emission tomography is associated with improved left ventricular ejection fraction in patients with cardiac sarcoidosis. J Nucl Cardiol. 2014;21:166–74.CrossRefGoogle Scholar
  6. 6.
    Koyanagawa K, Naya M, Aikawa T, Manabe O, Kuzume M, Ohira H, et al. Prognostic value of phase analysis on gated single photon emission computed tomography in patients with cardiac sarcoidosis. J Nucl Cardiol. 2019. Scholar
  7. 7.
    Surasi DS, Manapragada PP, Lloyd SG, Bhambhvani P. Role of multimodality imaging including Thallium-201 myocardial perfusion imaging in the diagnosis and monitoring of treatment response in cardiac sarcoidosis. J Nucl Cardiol. 2014;21:849–52.CrossRefGoogle Scholar
  8. 8.
    Aikawa T, Oyama-Manabe N, Naya M, Ohira H, Sugimoto A, Tsujino I, et al. Delayed contrast-enhanced computed tomography in patients with known or suspected cardiac sarcoidosis: A feasibility study. Eur Radiol. 2017;27:4054–63.CrossRefGoogle Scholar
  9. 9.
    Manabe O, Yoshinaga K, Ohira H, Masuda A, Sato T, Tsujino I, et al. The effects of 18-h fasting with low-carbohydrate diet preparation on suppressed physiological myocardial (18)F-fluorodeoxyglucose (FDG) uptake and possible minimal effects of unfractionated heparin use in patients with suspected cardiac involvement sarcoidosis. J Nucl Cardiol. 2016;23:244–52.CrossRefGoogle Scholar
  10. 10.
    Morooka M, Moroi M, Uno K, Ito K, Wu J, Nakagawa T, et al. Long fasting is effective in inhibiting physiological myocardial 18F-FDG uptake and for evaluating active lesions of cardiac sarcoidosis. EJNMMI Res. 2014;4:1.CrossRefGoogle Scholar
  11. 11.
    Ohira H, Tsujino I, Yoshinaga K. (1)(8)F-Fluoro-2-deoxyglucose positron emission tomography in cardiac sarcoidosis. Eur J Nucl Med Mol Imaging. 2011;38:1773–83.CrossRefGoogle Scholar
  12. 12.
    Ishimaru S, Tsujino I, Takei T, Tsukamoto E, Sakaue S, Kamigaki M, et al. Focal uptake on 18F-fluoro-2-deoxyglucose positron emission tomography images indicates cardiac involvement of sarcoidosis. Eur Heart J. 2005;26:1538–43.CrossRefGoogle Scholar
  13. 13.
    Ahmadian A, Brogan A, Berman J, Sverdlov AL, Mercier G, Mazzini M, et al. Quantitative interpretation of FDG PET/CT with myocardial perfusion imaging increases diagnostic information in the evaluation of cardiac sarcoidosis. J Nucl Cardiol. 2014;21:925–39.CrossRefGoogle Scholar
  14. 14.
    Manabe O, Kroenke M, Aikawa T, Murayama A, Naya M, Masuda A, et al. Volume-based glucose metabolic analysis of FDG PET/CT: The optimum threshold and conditions to suppress physiological myocardial uptake. J Nucl Cardiol. 2019;26:909–18.CrossRefGoogle Scholar
  15. 15.
    Hirata K, Kobayashi K, Wong KP, Manabe O, Surmak A, Tamaki N, et al. A semi-automated technique determining the liver standardized uptake value reference for tumor delineation in FDG PET-CT. PLoS ONE. 2014;9:e105682.CrossRefGoogle Scholar
  16. 16.
    Naya M, Manabe O, Koyanagawa K, Tamaki N. The role of nuclear medicine in assessments of cardiac dyssynchrony. J Nucl Cardiol. 2018;25:1980–7.CrossRefGoogle Scholar
  17. 17.
    Okuda K, Nakajima K, Matsuo S, Kashiwaya S, Yoneyama H, Shibutani T, et al. Comparison of diagnostic performance of four software packages for phase dyssynchrony analysis in gated myocardial perfusion SPECT. EJNMMI Res. 2017;7:27.CrossRefGoogle Scholar
  18. 18.
    Yuki H, Utsunomiya D, Shiraishi S, Takashio S, Sakamoto F, Tsuda N, et al. Correlation of left ventricular dyssynchrony on gated myocardial perfusion SPECT analysis with extent of late gadolinium enhancement on cardiac magnetic resonance imaging in hypertrophic cardiomyopathy. Heart Vessels. 2018;33:623–9.CrossRefGoogle Scholar
  19. 19.
    Nakajima K, Okuda K, Matsuo S, Kiso K, Kinuya S, Garcia EV. Comparison of phase dyssynchrony analysis using gated myocardial perfusion imaging with four software programs: Based on the Japanese Society of Nuclear Medicine working group normal database. J Nucl Cardiol. 2017;24:611–21.CrossRefGoogle Scholar
  20. 20.
    Okuda K, Nakajima K. What does entropy reveal in phase analysis of myocardial perfusion SPECT? J Nucl Cardiol. 2019. Scholar
  21. 21.
    Okumura W, Iwasaki T, Toyama T, Iso T, Arai M, Oriuchi N, et al. Usefulness of fasting 18F-FDG PET in identification of cardiac sarcoidosis. J Nucl Med. 2004;45:1989–98.PubMedGoogle Scholar
  22. 22.
    Le Guludec D, Menad F, Faraggi M, Weinmann P, Battesti JP, Valeyre D. Myocardial sarcoidosis. Clinical value of technetium-99m sestamibi tomoscintigraphy. Chest. 1994;106:1675–82.CrossRefGoogle Scholar
  23. 23.
    Chareonthaitawee P, Beanlands RS, Chen W, Dorbala S, Miller EJ, Murthy VL, et al. Joint SNMMI-ASNC expert consensus document on the role of (18)F-FDG PET/CT in cardiac sarcoid detection and therapy monitoring. J Nucl Cardiol. 2017;24:1741–58.CrossRefGoogle Scholar
  24. 24.
    Chiu CZ, Nakatani S, Zhang G, Tachibana T, Ohmori F, Yamagishi M, et al. Prevention of left ventricular remodeling by long-term corticosteroid therapy in patients with cardiac sarcoidosis. Am J Cardiol. 2005;95:143–6.CrossRefGoogle Scholar
  25. 25.
    Bengel FM, Ross TL. Emerging imaging targets for infiltrative cardiomyopathy: Inflammation and fibrosis. J Nucl Cardiol. 2019;26:208–16.CrossRefGoogle Scholar
  26. 26.
    Bussinguer M, Danielian A, Sharma OP. Cardiac sarcoidosis: Diagnosis and management. Curr Treat Options Cardiovasc Med. 2012;14:652–64.CrossRefGoogle Scholar
  27. 27.
    Yazaki Y, Isobe M, Hiroe M, Morimoto S, Hiramitsu S, Nakano T, et al. Prognostic determinants of long-term survival in Japanese patients with cardiac sarcoidosis treated with prednisone. Am J Cardiol. 2001;88:1006–10.CrossRefGoogle Scholar
  28. 28.
    Gradel C, Jain D, Batsford WP, Wackers FJ, Zaret BL. Relationship of scar and ischemia to the results of programmed electrophysiological stimulation in patients with coronary artery disease. J Nucl Cardiol. 1997;4:379–86.CrossRefGoogle Scholar

Copyright information

© American Society of Nuclear Cardiology 2019

Authors and Affiliations

  • Kazuhiro Koyanagawa
    • 1
  • Masanao Naya
    • 1
    Email author
  • Tadao Aikawa
    • 1
  • Osamu Manabe
    • 2
  • Sho Furuya
    • 2
  • Masato Kuzume
    • 1
  • Noriko Oyama-Manabe
    • 2
  • Hiroshi Ohira
    • 3
  • Ichizo Tsujino
    • 3
  • Toshihisa Anzai
    • 1
  1. 1.Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of MedicineHokkaido UniversitySapporoJapan
  2. 2.Department of Diagnostic and Interventional RadiologyHokkaido University HospitalSapporoJapan
  3. 3.First Department of MedicineHokkaido University HospitalSapporoJapan

Personalised recommendations