Skip to main content

Advertisement

Log in

Diagnosis of cardiac sarcoidosis: a primer for non-imagers

  • Published:
Heart Failure Reviews Aims and scope Submit manuscript

Abstract

Sarcoidosis is a multisystem granulomatous disorder that can potentially involve any organ. Cardiac involvement in sarcoidosis has been reported in up to 25% of patients based on autopsy and imaging studies. The gold standard for diagnosing cardiac sarcoidosis is endomyocardial biopsy demonstrating non-caseating granulomas; however, this technique lacks sensitivity due to the patchy nature of myocardial involvement. This, along with the non-specific clinical presentation, renders the diagnosis of cardiac sarcoidosis extremely challenging. Difficulties in obtaining histopathologic diagnosis and the advances in imaging modalities have led to a paradigm shift toward non-invasive imaging in the diagnosis of cardiac sarcoidosis. Advances in cardiac imaging modalities have also allowed unprecedented insights into the prevalence and natural history of cardiac sarcoidosis. This review discusses the role of non-invasive imaging for diagnosis, risk stratification, and monitoring the response to therapies in cardiac sarcoidosis. Echocardiography remains the first-line modality due to widespread availability and affordability. Cardiac magnetic resonance imaging (CMR) can be used to study cardiac structure, function, and most importantly tissue characterization to detect inflammation and fibrosis. Fluoro-deoxy glucose positron emission tomography (FDG PET) is the gold standard for non-invasive detection of cardiac inflammation, and it offers the unique ability to assess response to therapeutic interventions. Hybrid imaging is a promising technique that allows us to combine the unique strengths of CMR and FDG PET. Understanding the advantages and disadvantages of each of these imaging modalities is crucial in order to tailor the diagnostic algorithm and utilize the most appropriate modality for each patient.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

ATS:

American Thoracic Society

CMR:

Cardiac magnetic resonance imaging

EKG:

Electrocardiogram

EMB:

Endomyocardial biopsy

FDG:

Fluoro-deoxy glucose

HRS:

Heart Rhythm Society

JMHW:

Japanese Ministry of Health and Welfare

LGE:

Late gadolinium enhancement

LVEF:

Left ventricular ejection fraction

MPI:

Myocardial perfusion imaging

PET:

Positron emission tomography

SPECT:

Single positron emission tomography

TTE:

Trans-thoracic echocardiogram

References

  1. James DG, Sharma OP (2002) From Hutchinson to now: a historical glimpse. Curr Opin Pulm Med 8(5):416–423. https://doi.org/10.1097/00063198-200209000-00013

    Article  PubMed  Google Scholar 

  2. Iannuzzi MC, Rybicki BA (2007) Genetics of sarcoidosis: candidate genes and genome scans. Proc Am Thorac Soc 4(1):108–116. https://doi.org/10.1513/pats.200607-141JG

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Newman LS, Rose CS, Bresnitz EA et al (2004) A case control etiologic study of sarcoidosis: environmental and occupational risk factors. Am J Respir Crit Care Med 170(12):1324–1330. https://doi.org/10.1164/rccm.200402-249OC

    Article  PubMed  Google Scholar 

  4. Naruse TK, Matsuzawa Y, Ota M et al (2000) HLA-DQB1*0601 is primarily associated with the susceptibility to cardiac sarcoidosis. Tissue Antigens 56(1):52–57. https://doi.org/10.1034/j.1399-0039.2000.560107.x

  5. Takashige N, Naruse TK, Matsumori A et al (1999) Genetic polymorphisms at the tumour necrosis factor loci (TNFA and TNFB) in cardiac sarcoidosis. Tissue Antigens 54(2):191–193. https://doi.org/10.1034/j.1399-0039.1999.540211.x

    Article  CAS  PubMed  Google Scholar 

  6. Silverman KJ, Hutchins GM, Bulkley BH (1978) Cardiac sarcoid: a clinicopathologic study of 84 unselected patients with systemic sarcoidosis. Circulation 58(6):1204–1211. https://doi.org/10.1161/01.cir.58.6.1204

    Article  CAS  PubMed  Google Scholar 

  7. Iwai K, Takemura T, Kitaichi M, Kawabata Y, Matsui Y (1993) Pathological studies on sarcoidosis autopsy. II. Early change, mode of progression and death pattern. Acta Pathol Jpn 43(7–8):377–85. https://doi.org/10.1111/j.1440-1827.1993.tb01149.x

  8. Ungprasert P, Carmona EM, Utz JP, Ryu JH, Crowson CS, Matteson EL (2016) Epidemiology of Sarcoidosis 1946–2013: a population-based study. Mayo Clin Proc 91(2):183–188. https://doi.org/10.1016/j.mayocp.2015.10.024

    Article  PubMed  Google Scholar 

  9. Baughman RP, Teirstein AS, Judson MA et al (2001) Clinical characteristics of patients in a case control study of sarcoidosis. Am J Respir Crit Care Med 164(10 Pt 1):1885–1889. https://doi.org/10.1164/ajrccm.164.10.2104046

    Article  CAS  PubMed  Google Scholar 

  10. Iwai K, Tachibana T, Takemura T, Matsui Y, Kitaichi M, Kawabata Y (1993) Pathological studies on sarcoidosis autopsy. I. epidemiological features of 320 cases in Japan. Acta Pathol Jpn 43(7–8):372–376. https://doi.org/10.1111/j.1440-1827.1993.tb01148.x

  11. Perry A, Vuitch F (1995) Causes of death in patients with sarcoidosis. a morphologic study of 38 autopsies with clinicopathologic correlations. Arch Pathol Lab Med 119(2):167–172

  12. Lynch JP 3rd, Hwang J, Bradfield J, Fishbein M, Shivkumar K, Tung R (2014) Cardiac involvement in sarcoidosis: evolving concepts in diagnosis and treatment. Semin Respir Crit Care Med 35(3):372–390. https://doi.org/10.1055/s-0034-1376889

    Article  PubMed  PubMed Central  Google Scholar 

  13. Birnie DH, Nery PB, Ha AC, Beanlands RS (2016) Cardiac Sarcoidosis. J Am Coll Cardiol 68(4):411–421. https://doi.org/10.1016/j.jacc.2016.03.605

    Article  PubMed  Google Scholar 

  14. Kandolin R, Lehtonen J, Graner M et al (2011) Diagnosing isolated cardiac sarcoidosis. J Intern Med 270(5):461–468. https://doi.org/10.1111/j.1365-2796.2011.02396.x

    Article  CAS  PubMed  Google Scholar 

  15. Youssef G, Leung E, Mylonas I et al (2012) The use of 18F-FDG PET in the diagnosis of cardiac sarcoidosis: a systematic review and metaanalysis including the Ontario experience. J Nucl Med 53(2):241–248. https://doi.org/10.2967/jnumed.111.090662

    Article  CAS  PubMed  Google Scholar 

  16. Greulich S, Deluigi CC, Gloekler S et al (2013) CMR imaging predicts death and other adverse events in suspected cardiac sarcoidosis. JACC Cardiovasc Imaging 6(4):501–511. https://doi.org/10.1016/j.jcmg.2012.10.021

    Article  PubMed  Google Scholar 

  17. Kandolin R, Lehtonen J, Airaksinen J et al (2015) Cardiac sarcoidosis: epidemiology, characteristics, and outcome over 25 years in a nationwide study. Circulation 131(7):624–632. https://doi.org/10.1161/circulationaha.114.011522

    Article  PubMed  Google Scholar 

  18. Birnie DH, Sauer WH, Bogun F et al (2014) HRS expert consensus statement on the diagnosis and management of arrhythmias associated with cardiac sarcoidosis. Heart Rhythm 11(7):1305–1323. https://doi.org/10.1016/j.hrthm.2014.03.043

    Article  PubMed  Google Scholar 

  19. Yazaki Y, Isobe M, Hiroe M et al (2001) Prognostic determinants of long-term survival in Japanese patients with cardiac sarcoidosis treated with prednisone. Am J Cardiol 88(9):1006–1010. https://doi.org/10.1016/s0002-9149(01)01978-6

    Article  CAS  PubMed  Google Scholar 

  20. Roberts WC, Becker TM, Hall SA (2018) Usefulness of total 12-lead QRS voltage as a clue to diagnosis of patients with cardiac sarcoidosis severe enough to warrant orthotopic heart transplant. JAMA Cardiol 3(1):64–68. https://doi.org/10.1001/jamacardio.2017.4172

    Article  PubMed  Google Scholar 

  21. Cain MA, Metzl MD, Patel AR et al (2014) Cardiac sarcoidosis detected by late gadolinium enhancement and prevalence of atrial arrhythmias. Am J Cardiol 113(9):1556–1560. https://doi.org/10.1016/j.amjcard.2014.01.434

    Article  PubMed  Google Scholar 

  22. Okada DR, Smith J, Derakhshan A et al (2018) Ventricular arrhythmias in cardiac sarcoidosis. Circulation 138(12):1253–1264. https://doi.org/10.1161/circulationaha.118.034687

    Article  PubMed  Google Scholar 

  23. Naruse Y, Sekiguchi Y, Nogami A et al (2014) Systematic treatment approach to ventricular tachycardia in cardiac sarcoidosis. Circ Arrhythm Electrophysiol 7(3):407–413. https://doi.org/10.1161/circep.113.000734

    Article  PubMed  Google Scholar 

  24. Coleman GC, Shaw PW, Balfour PC Jr et al (2017) Prognostic value of myocardial scarring on CMR in patients with cardiac sarcoidosis. JACC Cardiovasc Imaging 10(4):411–420. https://doi.org/10.1016/j.jcmg.2016.05.009

    Article  PubMed  Google Scholar 

  25. Blankstein R, Osborne M, Naya M et al (2014) Cardiac positron emission tomography enhances prognostic assessments of patients with suspected cardiac sarcoidosis. J Am Coll Cardiol 63(4):329–336. https://doi.org/10.1016/j.jacc.2013.09.022

    Article  PubMed  Google Scholar 

  26. Litovsky SH, Burke AP, Virmani R (1996) Giant cell myocarditis: an entity distinct from sarcoidosis characterized by multiphasic myocyte destruction by cytotoxic T cells and histiocytic giant cells. Mod Pathol: an official journal of the United States and Canadian Academy of Pathology, Inc. 9(12):1126–34

  27. Fathima S, Roberts WC (2019) Comparison of clinical and morphologic findings in patients with cardiac sarcoidosis severe enough to warrant heart transplantation in those with -vs- those without non-caseating granulomas in the explanted heart (burnt-out sarcoid). Am J Cardiol 124(4):599–603. https://doi.org/10.1016/j.amjcard.2019.05.020

    Article  PubMed  Google Scholar 

  28. Ardehali H, Howard DL, Hariri A et al (2005) A positive endomyocardial biopsy result for sarcoid is associated with poor prognosis in patients with initially unexplained cardiomyopathy. Am Heart J 150(3):459–463. https://doi.org/10.1016/j.ahj.2004.10.006

    Article  PubMed  Google Scholar 

  29. Sekiguchi M, Hiroe M, Take M, Hirosawa K (1980) Clinical and histopathological profile of sarcoidosis of the heart and acute idiopathic myocarditis. concepts through a study employing endomyocardial biopsy. II. Myocarditis. Jpn Circ J 44(4):264–73. https://doi.org/10.1253/jcj.44.264

  30. Hiraga H, Yuwai K, Hiroe M (2007) Diagnostic standard and guidelines for sarcoidosis. Jpn J Sarcoidosis Granulomatous Disord 27:89–102

    Google Scholar 

  31. Terasaki F, Yoshinaga K (2017) New guidelines for diagnosis of cardiac sarcoidosis in Japan. Ann Nucl Cardiol 3(1):42–45. https://doi.org/10.17996/anc.17-00042

    Article  Google Scholar 

  32. Mehta D, Lubitz SA, Frankel Z et al (2008) Cardiac involvement in patients with sarcoidosis: diagnostic and prognostic value of outpatient testing. Chest 133(6):1426–1435. https://doi.org/10.1378/chest.07-2784

    Article  PubMed  Google Scholar 

  33. Crouser ED (2020) Diagnosis and detection of sarcoidosis. An official American Thoracic Society clinical practice guideline 201(8):e26–e51. https://doi.org/10.1164/rccm.202002-0251ST

  34. Bargout R, Kelly RF (2004) Sarcoid heart disease: clinical course and treatment. Int J Cardiol 97(2):173–182. https://doi.org/10.1016/j.ijcard.2003.07.024

    Article  PubMed  Google Scholar 

  35. Nureki S, Miyazaki E, Nishio S et al (2014) Interventricular septal thickening as an early manifestation of cardiac sarcoidosis. Int Heart J 55(2):181–183. https://doi.org/10.1536/ihj.13-243

    Article  PubMed  Google Scholar 

  36. Kurmann R, Mankad SV, Mankad R (2018) Echocardiography in sarcoidosis. Curr Cardiol Rep 20(11):118. https://doi.org/10.1007/s11886-018-1065-9

  37. Slart RH, Glaudemans AW, Lancellotti P, Hyafil F, Blankstein R, Schwartz RG, & Masci PG (2017) A joint procedural position statement on imaging in cardiac sarcoidosis: from the Cardiovascular and Inflammation & Infection Committees of the European Association of Nuclear Medicine, the European Association of Cardiovascular Imaging, and the American Society of Nuclear Cardiology. Eur Heart J Cardiovasc Imaging 18(10):1073–1089. https://doi.org/10.1093/ehjci/jex146

  38. Patel MB, Mor-Avi V, Murtagh G et al (2016) Right heart involvement in patients with sarcoidosis. Echocardiography (Mount Kisco, NY) 33(5):734–741. https://doi.org/10.1111/echo.13163

    Article  Google Scholar 

  39. Vasaiwala SC, Finn C, Delpriore J et al (2009) Prospective study of cardiac sarcoid mimicking arrhythmogenic right ventricular dysplasia. J Cardiovasc Electrophysiol 20(5):473–476. https://doi.org/10.1111/j.1540-8167.2008.01351.x

    Article  PubMed  Google Scholar 

  40. Aggarwal NR, Snipelisky D, Young PM, Gersh BJ, Cooper LT, Chareonthaitawee P (2015) Advances in imaging for diagnosis and management of cardiac sarcoidosis. Eur Heart J Cardiovasc Imaging 16(9):949–958. https://doi.org/10.1093/ehjci/jev142

    Article  PubMed  Google Scholar 

  41. Saleh Y, Abdelkarim O, Herzallah K, Abela GS (2020) Anthracycline-induced cardiotoxicity: mechanisms of action, incidence, risk factors, prevention, and treatment. Heart Fail Rev. https://doi.org/10.1007/s10741-020-09968-2

  42. Murtagh G, Laffin LJ, Patel KV et al (2016) Improved detection of myocardial damage in sarcoidosis using longitudinal strain in patients with preserved left ventricular ejection fraction. Echocardiography (Mount Kisco, NY) 33(9):1344–1352. https://doi.org/10.1111/echo.13281

    Article  Google Scholar 

  43. Felekos I, Aggeli C, Gialafos E et al (2018) Global longitudinal strain and long-term outcomes in asymptomatic extracardiac sarcoid patients with no apparent cardiovascular disease. Echocardiography (Mount Kisco, NY) 35(6):804–808. https://doi.org/10.1111/echo.13846

    Article  Google Scholar 

  44. Al-Mallah MH, Shareef MN (2011) The role of cardiac magnetic resonance imaging in the assessment of non-ischemic cardiomyopathy. Heart Fail Rev 16(4):369–380. https://doi.org/10.1007/s10741-010-9221-3

    Article  PubMed  Google Scholar 

  45. Patel MR, Cawley PJ, Heitner JF et al (2009) Detection of myocardial damage in patients with sarcoidosis. Circulation 120(20):1969–1977. https://doi.org/10.1161/circulationaha.109.851352

    Article  PubMed  PubMed Central  Google Scholar 

  46. Smedema JP, Snoep G, van Kroonenburgh MP et al (2005) Evaluation of the accuracy of gadolinium-enhanced cardiovascular magnetic resonance in the diagnosis of cardiac sarcoidosis. J Am Coll Cardiol 45(10):1683–1690. https://doi.org/10.1016/j.jacc.2005.01.047

    Article  PubMed  Google Scholar 

  47. Crawford T, Mueller G, Sarsam S et al (2014) Magnetic resonance imaging for identifying patients with cardiac sarcoidosis and preserved or mildly reduced left ventricular function at risk of ventricular arrhythmias. Circ Arrhythm Electrophysiol 7(6):1109–1115. https://doi.org/10.1161/circep.113.000156

    Article  PubMed  Google Scholar 

  48. Aljizeeri A, Sulaiman A, Alhulaimi N, Alsaileek A, Al-Mallah MH (2017) Cardiac magnetic resonance imaging in heart failure: where the alphabet begins! Heart Fail Rev 22(4):385–399. https://doi.org/10.1007/s10741-017-9609-4

    Article  PubMed  Google Scholar 

  49. Nishiyama Y, Yamamoto Y, Fukunaga K et al (2006) Comparative evaluation of 18F-FDG PET and 67Ga scintigraphy in patients with sarcoidosis. J Nucl Med 47(10):1571–1576

    PubMed  Google Scholar 

  50. Yamagishi H, Shirai N, Takagi M et al (2003) Identification of cardiac sarcoidosis with (13)N-NH(3)/(18)F-FDG PET. J Nucl Med 44(7):1030–1036

    PubMed  Google Scholar 

  51. El-Tallawi KC, Parikh R, Nabi F, Maclayton PI, Trachtenberg BH, Al-Mallah M (2020) A positive Tc-99m PYP scan in a patient with cardiac sarcoidosis. J Nucl Cardiol. https://doi.org/10.1007/s12350-020-02158-5

  52. Treglia G, Annunziata S, Sobic-Saranovic D, Bertagna F, Caldarella C, Giovanella L (2014) The role of 18F-FDG-PET and PET/CT in patients with sarcoidosis: an updated evidence-based review. Acad Radiol 21(5):675–684. https://doi.org/10.1016/j.acra.2014.01.008

    Article  PubMed  Google Scholar 

  53. Dorbala S, Di Carli MF, Delbeke D et al (2013) SNMMI/ASNC/SCCT guideline for cardiac SPECT/CT and PET/CT 1.0. J Nucl Med 54(8):1485–1507. https://doi.org/10.2967/jnumed.112.105155

  54. Scholtens AM, Verberne HJ, Budde RP, Lam MG (2016) Additional heparin preadministration improves cardiac glucose metabolism suppression over low-carbohydrate diet alone in 18F-FDG PET imaging. J Nucl Med 57(4):568–573. https://doi.org/10.2967/jnumed.115.166884

    Article  CAS  PubMed  Google Scholar 

  55. Okumura W, Iwasaki T, Toyama T et al (2004) Usefulness of fasting 18F-FDG PET in identification of cardiac sarcoidosis. J Nucl Med 45(12):1989–1998

    PubMed  Google Scholar 

  56. Khalaf S, Al-Mallah MH (2020) Fluorodeoxyglucose applications in cardiac PET: viability, inflammation, infection, and beyond. Methodist Debakey Cardiovasc J 16(2):122–129. https://doi.org/10.14797/mdcj-16-2-122

    Article  PubMed  PubMed Central  Google Scholar 

  57. Osborne MT, Hulten EA, Murthy VL et al (2017) Patient preparation for cardiac fluorine-18 fluorodeoxyglucose positron emission tomography imaging of inflammation. J Nucl Cardiol 24(1):86–99. https://doi.org/10.1007/s12350-016-0502-7

    Article  PubMed  Google Scholar 

  58. Osborne MT, Hulten EA, Singh A et al (2014) Reduction in 18 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 21(1):166–174. https://doi.org/10.1007/s12350-013-9828-6

    Article  PubMed  Google Scholar 

  59. Rosenthal DG, Parwani P, Murray TO et al (2019) Long-term corticosteroid-sparing immunosuppression for cardiac sarcoidosis. J Am Heart Assoc 8(18):e010952. https://doi.org/10.1161/jaha.118.010952

  60. Nekolla SG, Martinez-Moeller A, Saraste A (2009) PET and MRI in cardiac imaging: from validation studies to integrated applications. Eur J Nucl Med Mol Imaging 36(Suppl 1):S121–S130. https://doi.org/10.1007/s00259-008-0980-1

    Article  PubMed  Google Scholar 

  61. Dweck MR, Abgral R, Trivieri MG et al (2018) Hybrid magnetic resonance imaging and positron emission tomography with fluorodeoxyglucose to diagnose active cardiac sarcoidosis. JACC Cardiovasc Imaging 11(1):94–107. https://doi.org/10.1016/j.jcmg.2017.02.021

    Article  PubMed  Google Scholar 

  62. Vita T, Okada DR, Veillet-Chowdhury M et al (2018) Complementary value of cardiac magnetic resonance imaging and positron emission tomography/computed tomography in the assessment of cardiac sarcoidosis. Circ Cardiovasc Imaging 11(1):e007030. https://doi.org/10.1161/circimaging.117.007030

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mouaz Al-Mallah.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Agrawal, T., Saleh, Y., Sukkari, M.H. et al. Diagnosis of cardiac sarcoidosis: a primer for non-imagers. Heart Fail Rev 27, 1223–1233 (2022). https://doi.org/10.1007/s10741-021-10126-5

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10741-021-10126-5

Keywords

Navigation