Abstract
Cardiac sarcoidosis (CS) remains an intriguing infiltrating disorder and one of the most important forms of inflammatory cardiomyopathy. Identification of patients with CS is of extreme importance because they are at higher risk of sudden death, and heart-failure progression. And while it remains a diagnostic conundrum, a great amount of experience has been accumulated over the last decade with the advent of fluorine-18 fluorodeoxyglucose positron emission tomography and cardiac magnetic resonance with late gadolinium enhancement imaging. They have both proven to be advanced imaging techniques that provide important, and often complementary, diagnostic and prognostic information for the management of CS. However, they have also shown to have limitations, and, thus, there is a continued need for developing more specific imaging probes for identifying cardiac inflammation. The aim of the present manuscript is to provide the reader with a better understanding of the histopathology of the disease, how this potentially relates to noninvasive imaging detection, and the best strategies available for the diagnosis and management of patients with CS.
Similar content being viewed by others
Abbreviations
- CS:
-
Cardiac sarcoidosis
- CMR:
-
Cardiac magnetic resonance imaging
- FDG:
-
Fluorine-18 fluorodeoxyglucose
- PET:
-
Positron emission tomography
- LGE:
-
Late gadolinium enhancement
References
Longcope WT, Freiman DG. A study of sarcoidosis; based on a combined investigation of 160 cases including 30 autopsies from The Johns Hopkins Hospital and Massachusetts General Hospital. Medicine (Baltim) 1952;31:1-132.
Silverman KJ, Hutchins GM, Bulkley BH. Cardiac sarcoid: A clinicopathologic study of 84 unselected patients with systemic sarcoidosis. Circulation 1978;58:1204-11.
Sharma OP, Maheshwari A, Thaker K. Myocardial sarcoidosis. Chest 1993;103:253-8.
Matsui Y, Iwai K, Tachibana T, et al. Clinicopathological study of fatal myocardial sarcoidosis. Ann NY Acad Sci 1976;278:455-69.
Pierre-Louis B, Prasad A, Frishman WH. Cardiac manifestations of sarcoidosis and therapeutic options. Cardiol Rev 2009;17:153-8.
Roberts WC, McAllister HA Jr, Ferrans VJ. Sarcoidosis of the heart. A clinicopathologic study of 35 necropsy patients (group 1) and review of 78 previously described necropsy patients (group 11). Am J Med 1977;63:86-108.
Epstein AE, DiMarco JP, Ellenbogen KA, et al. ACC/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices): Developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons. Circulation 2008;117:e350-408.
Kron J, Sauer W, Schuller J, et al. Efficacy and safety of implantable cardiac defibrillators for treatment of ventricular arrhythmias in patients with cardiac sarcoidosis. Europace Eur Pacing Arrhythm Card Electrophysiol J Work Groups Card Pacing Arrhythm Card Cell Electrophysiol Eur Soc Cardiol 2013;15:347-54.
Hiramitsu S, Morimoto S, Uemura A, et al. National survey on status of steroid therapy for cardiac sarcoidosis in Japan. Sarcoidosis Vasc Diffus Lung Dis 2005;22:210-3.
Birnie DH, Sauer WH, Bogun F, et al. HRS expert consensus statement on the diagnosis and management of arrhythmias associated with cardiac sarcoidosis. Heart Rhythm Off J Heart Rhythm Soc 2014;11:1305-23.
Chareonthaitawee P, Beanlands RS, Chen W, 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 Off Publ Am Soc Nucl Cardiol 2017;24:1741-58.
Writing Group, Document Reading Group, EACVI Reviewers. A joint procedural position statement on imaging in cardiac sarcoidosis: From the Cardiovascular and Inflammation and 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 2017;18:1073-89.
Uemura A, Morimoto S, Hiramitsu S, Kato Y, Ito T, Hishida H. Histologic diagnostic rate of cardiac sarcoidosis: Evaluation of endomyocardial biopsies. Am Heart J 1999;138:299-302.
Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl J Med 2007;357:2153-65.
Deckers JW, Hare JM, Baughman KL. Complications of transvenous right ventricular endomyocardial biopsy in adult patients with cardiomyopathy: A seven-year survey of 546 consecutive diagnostic procedures in a tertiary referral center. J Am Coll Cardiol 1992;19:43-7.
Okumura W, Iwasaki T, Toyama T, et al. Usefulness of fasting 18F-FDG PET in identification of cardiac sarcoidosis. J Nucl Med Off Publ Soc Nucl Med 2004;45:1989-98.
Greulich S, Deluigi CC, Gloekler S, et al. CMR imaging predicts death and other adverse events in suspected cardiac sarcoidosis. JACC Cardiovasc Imaging 2013;6:501-11.
Tavora F, Cresswell N, Li L, Ripple M, Solomon C, Burke A. Comparison of necropsy findings in patients with sarcoidosis dying suddenly from cardiac sarcoidosis versus dying suddenly from other causes. Am J Cardiol 2009;104:571-7.
Thomson AD. The pathology of sarcoidosis. Postgrad Med J 1958;34:248-53.
Poulter LW. Immune aspects of sarcoidosis. Postgrad Med J 1988;64:536-43.
Nihoyannopoulos P, Dawson D. Restrictive cardiomyopathies. Eur J Echocardiogr 2009;10:iii23-33.
Agarwal A, Sulemanjee NZ, Cheema O, Downey FX, Tajik AJ. Cardiac sarcoid: A chameleon masquerading as hypertrophic cardiomyopathy and dilated cardiomyopathy in the same patient. Echocardiography 2014;31:E138-41.
Adlan AM, Prasad SK, Varnava AM. Sarcoidosis presenting as dilated cardiomyopathy. Heart 2011;97:1896.
Patel AR, Klein MR, Chandra S, et al. Myocardial damage in patients with sarcoidosis and preserved left ventricular systolic function: An observational study. Eur J Heart Fail 2011;13:1231-7.
Freeman AM, Curran-Everett D, Weinberger HD, et al. Predictors of cardiac sarcoidosis using commonly available cardiac studies. Am J Cardiol 2013;112:280-5.
Kouranos V, Tzelepis GE, Rapti A, et al. Complementary role of CMR to conventional screening in the diagnosis and prognosis of cardiac sarcoidosis. JACC Cardiovasc Imaging 2017;10:1437-47.
Mehta D, Lubitz SA, Frankel Z, et al. Cardiac involvement in patients with sarcoidosis: Diagnostic and prognostic value of outpatient testing. Chest 2008;133:1426-35.
Okumura W, Iwasaki T, Ueda T, et al. Usefulness of 18F-FDG PET for diagnosis of cardiac sarcoidosis. Kaku Igaku 1999;36:341-8.
Ohira H, Tsujino I, Ishimaru S, et al. Myocardial imaging with 18F-fluoro-2-deoxyglucose positron emission tomography and magnetic resonance imaging in sarcoidosis. Eur J Nucl Med Mol Imaging 2008;35:933-41.
Smedema JP, Snoep G, van Kroonenburgh MP, et al. Evaluation of the accuracy of gadolinium-enhanced cardiovascular magnetic resonance in the diagnosis of cardiac sarcoidosis. J Am Coll Cardiol 2005;45:1683-90.
Youssef G, Leung E, Mylonas I, et al. The use of 18F-FDG PET in the diagnosis of cardiac sarcoidosis: A systematic review and metaanalysis including the Ontario experience. J Nucl Med Off Publ Soc Nucl Med 2012;53:241-8.
Okada DR, Bravo PE, Vita T, et al. Isolated cardiac sarcoidosis: A focused review of an under-recognized entity. J Nucl Cardiol Off Publ Am Soc Nucl Cardiol 2016. https://doi.org/10.1007/s12350-016-0658-1.
Sperry BW, Oldan J, Hachamovitch R, Tamarappoo BK. Insights into biopsy-proven cardiac sarcoidosis in patients with heart failure. J Heart Lung Transplant Off Publ Int Soc Heart Transplant 2015. https://doi.org/10.1016/j.healun.2015.12.005.
Osborne MT, Hulten EA, Singh A, 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 Off Publ Am Soc Nucl Cardiol 2014;21:166-74.
Blankstein R, Osborne M, Naya M, et al. Cardiac positron emission tomography enhances prognostic assessments of patients with suspected cardiac sarcoidosis. J Am Coll Cardiol 2014;63:329-36.
Orii M, Hirata K, Tanimoto T, et al. Comparison of cardiac MRI and 18F-FDG positron emission tomography manifestations and regional response to corticosteroid therapy in newly diagnosed cardiac sarcoidosis with complete heart block. Heart Rhythm Off J Heart Rhythm Soc 2015;12:2477-85.
Osborne MT, Hulten EA, Murthy VL, et al. Patient preparation for cardiac fluorine-18 fluorodeoxyglucose positron emission tomography imaging of inflammation. J Nucl Cardiol Off Publ Am Soc Nucl Cardiol 2016. https://doi.org/10.1007/s12350-016-0502-7.
Sibille L, Chambert B, Collombier L, Kotzki PO, Boudousq V. False positive 18F-FDG PET/CT in cardiac sarcoidosis. J Mol Biol Mol Imaging 2015;2:1020.
Mielniczuk LM, Birnie D, Ziadi MC, et al. Relation between right ventricular function and increased right ventricular [18F]fluorodeoxyglucose accumulation in patients with heart failure. Circ Cardiovasc Imaging 2011;4:59-66.
Nakayama T, Sugano Y, Yokokawa T, et al. Clinical impact of the presence of macrophages in endomyocardial biopsies of patients with dilated cardiomyopathy. Eur J Heart Fail 2017;19:490-8.
Huang B, Law MW, Khong PL. Whole-body PET/CT scanning: Estimation of radiation dose and cancer risk. Radiology 2009;251:166-74.
Kim RJ, Chen EL, Lima JA, Judd RM. Myocardial Gd-DTPA kinetics determine MRI contrast enhancement and reflect the extent and severity of myocardial injury after acute reperfused infarction. Circulation1996;94:3318-26.
Moraes GL, Higgins CB, Ordovas KG. Delayed enhancement magnetic resonance imaging in nonischemic myocardial disease. J Thorac Imaging 2013;28:84-92; quiz 93-5.
Vita T, Okada DR, Veillet-Chowdhury M, et al. Complementary value of cardiac magnetic resonance imaging and positron emission tomography/computed tomography in the assessment of cardiac sarcoidosis. Circ Cardiovasc Imaging 2018;11:e007030.
Patel MR, Cawley PJ, Heitner JF, et al. Detection of myocardial damage in patients with sarcoidosis. Circulation 2009;120:1969-77.
Hulten E, Agarwal V, Cahill M, et al. Presence of late gadolinium enhancement by cardiac magnetic resonance among patients with suspected cardiac sarcoidosis is associated with adverse cardiovascular prognosis: A systematic review and meta-analysis. Circ Cardiovasc Imaging 2016;9:e005001.
Ferreira PF, Gatehouse PD, Mohiaddin RH, Firmin DN. Cardiovascular magnetic resonance artefacts. J Cardiovasc Magn Reson 2013;15:41.
Blankstein R, Waller AH. Evaluation of known or suspected cardiac sarcoidosis. Circ Cardiovasc Imaging 2016;9:e000867.
Bernstein EJ, Schmidt-Lauber C, Kay J. Nephrogenic systemic fibrosis: A systemic fibrosing disease resulting from gadolinium exposure. Best Pract Res Clin Rheumatol 2012;26:489-503.
Crouser ED, Ono C, Tran T, He X, Raman SV. Improved detection of cardiac sarcoidosis using magnetic resonance with myocardial T2 mapping. Am J Respir Crit Care Med 2014;189:109-12.
Crouser ED, Ruden E, Julian MW, Raman SV. Resolution of abnormal cardiac MRI T2 signal following immune suppression for cardiac sarcoidosis. J Investig Med 2016;64:1148-50.
Dweck MR, Abgral R, Trivieri MG, et al. Hybrid magnetic resonance imaging and positron emission tomography with fluorodeoxyglucose to diagnose active cardiac sarcoidosis. JACC Cardiovasc Imaging 2017. https://doi.org/10.1016/j.jcmg.2017.02.021.
Bravo PE, Raghu G, Rosenthal DG, et al. Risk assessment of patients with clinical manifestations of cardiac sarcoidosis with positron emission tomography and magnetic resonance imaging. Int J Cardiol 2017;241:457-62.
Ohira H, Birnie DH, Pena E, et al. Comparison of (18)F-fluorodeoxyglucose positron emission tomography (FDG PET) and cardiac magnetic resonance (CMR) in corticosteroid-naive patients with conduction system disease due to cardiac sarcoidosis. Eur J Nucl Med Mol Imaging 2016;43:259-69.
van Hagen PM. Somatostatin receptor expression in clinical immunology. Metabolism 1996;45:86-7.
ten Bokum AM, Hofland LJ, de Jong G, et al. Immunohistochemical localization of somatostatin receptor sst2A in sarcoid granulomas. Eur J Clin Investig 1999;29:630-6.
Balon HR, Goldsmith SJ, Siegel BA, et al. Procedure guideline for somatostatin receptor scintigraphy with (111)In-pentetreotide. J Nucl Med Off Publ Soc Nucl Med 2001;42:1134-8.
Bombardieri E, Ambrosini V, Aktolun C, et al. 111In-pentetreotide scintigraphy: Procedure guidelines for tumour imaging. Eur J Nucl Med Mol Imaging 2010;37:1441-8.
Kwekkeboom DJ, Krenning EP, Kho GS, Breeman WA, Van Hagen PM. Somatostatin receptor imaging in patients with sarcoidosis. Eur J Nucl Med 1998;25:1284-92.
Lebtahi R, Crestani B, Belmatoug N, et al. Somatostatin receptor scintigraphy and gallium scintigraphy in patients with sarcoidosis. J Nucl Med Off Publ Soc Nucl Med 2001;42:21-6.
Vanhagen PM, Krenning EP, Reubi JC, et al. Somatostatin analogue scintigraphy in granulomatous diseases. Eur J Nucl Med 1994;21:497-502.
Nobashi T, Nakamoto Y, Kubo T, et al. The utility of PET/CT with 68Ga-DOTATOC in sarcoidosis: Comparison with 67Ga-scintigraphy. Ann Nucl Med 2016. https://doi.org/10.1007/s12149-016-1095-6.
Lapa C, Reiter T, Li X, et al. Imaging of myocardial inflammation with somatostatin receptor based PET/CT—A comparison to cardiac MRI. Int J Cardiol 2015;194:44-9.
Reiter T, Werner RA, Bauer WR, Lapa C. Detection of cardiac sarcoidosis by macrophage-directed somatostatin receptor 2-based positron emission tomography/computed tomography. Eur Heart J 2015;36:2404.
Gormsen LC, Haraldsen A, Kramer S, Dias AH, Kim WY, Borghammer P. A dual tracer (68)Ga-DOTANOC PET/CT and (18)F-FDG PET/CT pilot study for detection of cardiac sarcoidosis. EJNMMI Res 2016;6:52.
Smedema JP, van Kroonenburgh MJ, Snoep G, Backes W, Gorgels AP. Images in cardiovascular medicine. Cardiac sarcoidosis in a patient with hypertrophic cardiomyopathy demonstrated by magnetic resonance imaging and single photon emission computed tomography dual-isotope scintigraphy. Circulation 2004;110:e529-31.
Shields AF, Grierson JR, Dohmen BM, et al. Imaging proliferation in vivo with [F-18]FLT and positron emission tomography. Nat Med 1998;4:1334-6.
van der Gaag RD, van Maarsseveen AC, Broekhuizen-Davies JM, Stam J. Application of in vitro techniques to determine proliferation in human sarcoid lymph nodes. J Pathol 1983;139:239-45.
Zhao S, Kuge Y, Kohanawa M, et al. Usefulness of 11C-methionine for differentiating tumors from granulomas in experimental rat models: A comparison with 18F-FDG and 18F-FLT. J Nucl Med Off Publ Soc Nucl Med 2008;49:135-41.
Kim SK, Im HJ, Kim W, Kim TS, Hwangbo B, Kim HJ. F-18 fluorodeoxyglucose and F-18 fluorothymidine positron emission tomography/computed tomography imaging in a case of neurosarcoidosis. Clin Nucl Med 2010;35:67-70.
Norikane T, Yamamoto Y, Maeda Y, Noma T, Nishiyama Y. 18F-FLT PET imaging in a patient with sarcoidosis with cardiac involvement. Clin Nucl Med 2015;40:433-4.
Norikane T, Yamamoto Y, Maeda Y, Noma T, Dobashi H, Nishiyama Y. Comparative evaluation of (18)F-FLT and (18)F-FDG for detecting cardiac and extra-cardiac thoracic involvement in patients with newly diagnosed sarcoidosis. EJNMMI Res 2017;7:69.
Acknowledgments
This work was supported in part by a grant from the National Institutes of Health (1T32HL094301, Dr. Bravo).
Disclosure
The authors have no conflict of interest to disclose.
Author information
Authors and Affiliations
Corresponding author
Additional information
The authors of this article have provided a PowerPoint file, available for download at SpringerLink, which summarises the contents of the paper and is free for re-use at meetings and presentations. Search for the article DOI on SpringerLink.com.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Bravo, P.E., Singh, A., Di Carli, M.F. et al. Advanced cardiovascular imaging for the evaluation of cardiac sarcoidosis. J. Nucl. Cardiol. 26, 188–199 (2019). https://doi.org/10.1007/s12350-018-01488-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12350-018-01488-9