Sarcoidosis is a multi-factorial inflammatory illness characterised by the formation of non-caseating granulomas within the affected organs. Cardiac involvement will be the primary, and sometimes the one, manifestation of sarcoidosis. The prevalence of cardiac sarcoidosis (CS) is increased than beforehand suspected. CS is related to elevated morbidity and mortality. Thus, early prognosis is important to introducing immunosuppressive remedy that would forestall an hostile final result. Endomyocardial biopsy (EMB) has restricted utility within the diagnostic pathway of sufferers with suspected CS. Consequently, superior imaging modalities, i.e. cardiac magnetic resonance imaging (MRI) and positron emission tomography with 18F-Fluorodeoxyglucose/computed tomography scan (18F-FDG-PET/CT), have emerged as different instruments for diagnosing CS and may be thought of the brand new ‘gold commonplace’. This centered evaluate will talk about the epidemiology and pathology of CS, when to suspect and consider CS, spotlight the complementary roles of cardiac MRI and 18F-FDG-PET/CT, and their diagnostic and prognostic values in CS, within the present content material of pointers for the diagnostic workflow of CS.
Introduction
Cardiac sarcoidosis (CS) is related to elevated morbidity and mortality.1 Thus, early prognosis is essential to introducing immunosuppressive remedy that would forestall an hostile final result.2 This centered evaluate will talk about the pathology of CS, when to suspect and consider CS, and spotlight the roles of superior imaging modalities, i.e. cardiac magnetic resonance imaging (MRI) and positron emission tomography (PET) with 18F-Fluorodeoxyglucose/computed tomography (CT) scan (18F-FDG-PET/CT), and their diagnostic and prognostic values in CS within the present content material of pointers for the diagnostic workflow of CS.3
Epidemiology and scientific presentation
CS happens in lower than 5% of sufferers with clinically manifested pulmonary/systemic sarcoidosis.4 Nevertheless, 27% of autopsied sarcoidosis sufferers from the US had cardiac involvement.5 The prevalence was as excessive as 39% in sarcoidosis sufferers with signs (palpitations, pre-syncope, or syncope) or irregular outcomes (electrocardiogram [ECG], Holter monitoring, and transthoracic echocardiography [TTE]) when studied with cardiac MRI or PET.6
Cardiac involvement could vary from silent myocardial granulomas to symptomatic conduction disturbances, ventricular arrhythmias, progressive coronary heart failure and sudden cardiac demise (SCD).7
Histopathology
The histological hallmark of sarcoidosis is the formation of non-caseating epithelioid granulomas within the affected organs.8 Sarcoid granuloma consists of a central core surrounded by primarily CD4+ T lymphocytes. The core consists of macrophages and multi-nucleate large cells, that are fused macrophages surrounded by giant macrophages referred to as epithelioid cells.9
At an early stage, lymphocyte numbers are noticeable, however the numbers decline with illness development. The granuloma/fibrosis preferentially impacts the sub-epicardial portion of the left ventricular (LV) free wall, adopted by the basal interventricular septum and the correct ventricle.10 Post-mortem of SCD instances resulting from undiagnosed CS confirmed the co-presence of dense fibrosis and lymphocytic infiltration generally.11
Diagnostic method
The general diagnostic yield of endomyocardial biopsy (EMB) is low.12 Additionally, EMB will not be appropriate for remedy monitoring.13 Consequently, cardiac MRI and 18F-FDG-PET/CT have emerged as different instruments for diagnosing CS, and may be thought of the brand new ‘gold commonplace’.
It’s advisable to display screen all sufferers with extracardiac sarcoidosis with an ECG14 and TTE with longitudinal pressure analysis15 (determine 1). Conduction abnormalities are related to elevated SCD.16 As well as, sufferers with irregular ECG or cardiac signs (e.g. palpitations, pre-syncope, syncope) ought to obtain additional diagnostic testing, i.e. serum N-terminal of the prohormone mind natriuretic peptide (NT-proBNP),17 high-sensitivity cardiac troponin T (hs-cTnT),18 ambulatory ECG monitoring,19 cardiac MRI,20 and 18F-FDG-PET/CT21 (determine 2). Restricted information recommend that early immunosuppressive therapy (<1 month from prognosis) might be related to a greater final result.22 Subsequently, an early investigational work-up is warranted.
TTE options suggestive of CS embody regional wall movement abnormality, wall aneurysm, basal septum wall thinning, diminished left ventricular ejection fraction (LVEF) <50%, and irregular longitudinal pressure.19 As well as, the TTE sensitivity and specificity for the prognosis of CS had been 10–47% and 82–92%, respectively.3 Thus, the first position of TTE is to find out and observe LV operate.3
![AlHayja - Figure 2. An algorithm for diagnosing clinically suspected cardiac sarcoidosis (CS)](https://bjcardio.co.uk/wp-content/uploads/2023/01/AlHayja-Figure-2-2023.01.04.png)
Cardiac MRI (CMR)
The primary power of cardiac MRI in diagnosing CS is figuring out patchy foci of late gadolinium enhancement (LGE) within the myocardium.23 The distribution of the LGE foci is often sub-epicardial or mid-myocardial (non-ischaemic sample) and alongside the correct ventricular insertion factors.24 As well as, the presence of LGE is related to elevated all-cause mortality and ventricular arrhythmia in CS.25
Gadolinium is an extracellular distinction agent with a speedy washout from regular areas of the traditional myocardium. Nevertheless, scar or extracellular growth resulting from irritation can increase the extracellular area and end in a slower washout of gadolinium, resulting in elevated T1-signal enhancement. A standard error is that LGE all the time means an irreversible scar.12 Subsequently, LGE alone is inadequate to tell apart between energetic and non-active illness (determine 3).26 T2-weighted imaging can detect oedema/irritation however suffers from low sensitivity resulting from low signal-to-noise ratio and artefacts.3 The general sensitivity and specificity of CMR-LGE for diagnosing CS had been 93% and 85%, respectively.27
![AlHayja - Figure 3. A 51-year-old man with cardiac and pulmonary sarcoidosis. Holter ECG revealed non-sustained ventricular tachycardia (VT) (not shown). An invasive coronary angiogram showed non-obstructive coronary arteries (not shown). Images A (apical four-chamber) and B (apical short-axis) represent cardiac magnetic resonance imaging (MRI) with a non-ischaemic distribution pattern of late gadolinium enhancement (LGE) in the apical inferoseptal and inferior segments (yellow arrows). Images C, D, and E represent the <sup>18</sup>F-fluorodeoxyglucose positron emission tomography/computed tomography (<sup>18</sup>F-FDG-PET/CT) imaging with focal <sup>18</sup>F-FDG uptake in the apical region of the myocardium and mediastinal lymph nodes (yellow arrows). Subsequently, he underwent endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) of the mediastinal lymph nodes, and the histopathology showed non-caseating granulomas. Images F, G, and H represent <sup>18</sup>F-FDG-PET/CT imaging after six months of immunosuppressive treatment with prednisolone and methotrexate with complete resolution of the focal <sup>18</sup>F-FDG uptake in the apical region of the myocardium and mediastinal lymph nodes](https://bjcardio.co.uk/wp-content/uploads/2023/01/Figure-3-2023.01.10.jpg)
18F-FDG-PET/CT scanning
Correct affected person preparation is important to suppress myocardial glucose uptake and higher visualise 18F-FDG uptake within the affected myocardium, i.e. extended fasting, high-fat, low-carbohydrate weight-reduction plan, and probably intravenous heparin administration.28 Subsequently, 18F-FDG-PET needs to be carried out at skilled centres.29 The general sensitivity and specificity of 18F-FDG-PET or PET/CT had been 84% and 83%, respectively, however with important heterogeneity of the included research, almost definitely because of the preparation protocols used.30 Irregular 18F-FDG-PET discovering was related to an elevated danger of main hostile cardiovascular occasions (MACE).31
Moreover, 18F-FDG-PET has a important position in serial monitoring of sufferers throughout remedy to determine responders and non-responders, so as to filter out the sufferers who could profit from immunosuppressive intensification or tapering (determine 3).32 Additional, a lower in 18F-FDG uptake was considerably related to fewer MACE at long-term follow-up.33
Restricted information exist on the timing of serial follow-up in sufferers with optimistic 18F-FDG-PET/CT scan. Nonetheless, a number of research and case studies confirmed that an early response after three months of the initiation of the immunosuppressive remedy might be noticed.34 Subsequently, serial imaging at three, six, and 12 months appears cheap. The primary drawback of 18F-FDG-PET/CT is the comparatively excessive price, radiation publicity, and 10% to fifteen% of 18F-FDG-PET scans shall be inconclusive.28
18F-FDG-PET/CT versus CMR, or each
The professionals and cons of CMR and 18F-FDG-PET/CT are summarised in desk 1.
Desk 1. Comparability between cardiac magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT)
Cardiac MRI
18F-FDG-PET/CT
Availability
+++
+
Price
++
+++
Requirement for particular preparation
–
+++
Sensitivity and specificity
+++
++
Radiation publicity
–
+
Cardiac morphology and performance
+++
–
Detecting energetic irritation
(–/+): with oedema sequence (T2 weighted), however unreliable(++): solely dependable with T2 mapping, however extra research are wanted
+++
Detecting extracardiac exercise
+++
Evaluation of therapy response
(+): solely dependable with T2 mapping, however extra research are wanted
+++
eGFR ≤30 ml/min/1.73 m2
(–): contraindicated(++): native T1 and T2 mapping can nonetheless be used
+++
Sufferers with implantable cardiac units
++
+++
Prognostic worth
+++
+++
Non-diagnostic outcome
Uncommon
In approx. 10% to fifteen% of scans
Key: eGFR = estimated glomerular filtration price
Contemplating that LGE can not distinguish between energetic and non-active illness,3518F-FDG-PET/CT is best in detecting the energetic section of CS, and permits the clinician to resolve on the initiation of immunosuppressive therapy (determine 3).3,21 Moreover, it’s also higher in figuring out extracardiac exercise (determine 3), which is current in 97% of sufferers with CS, and offering a biopsy goal.36 Thus, 18F-FDG-PET/CT is the strategy of alternative to observe and modify immunosuppressive remedy in CS (determine 3).3 Moreover, 18F-FDG-PET/CT will be utilised in sufferers with severely diminished persistent kidney illness, and it’s the popular scan in sufferers with implantable cardiac units.3 Alternatively, CMR is extensively out there, with increased sensitivity and detrimental predictive worth, and the presence and extent of LGE have essential prognostic implications.3,37,38
The European Society of Cardiology (ESC) and the American Thoracic Society (ATS) suggest performing CMR earlier than 18F-FDG-PET scan in sufferers with suspected cardiac involvement. Nevertheless, each societies emphasised the complementary worth of those assessments to extend diagnostic yield and assess for fibrosis and irritation.3,20
Conclusion
The diagnostic method in sufferers with clinically suspected CS ought to embody the cardiac serum markers (NT-proBNP and hs-cTnT), ECG, ambulatory ECG monitoring, TTE with longitudinal pressure evaluation, and cardiac MRI. If cardiac MRI findings are regular and the scientific suspicion of CS is low, no additional imaging is beneficial. Alternatively, if cardiac MRI is irregular or the scientific suspicion is excessive regardless of regular MRI outcomes, then 18F-FDG-PET/CT needs to be utilised. If 18F-FDG-PET/CT is diagnostic and optimistic, then immunosuppressive therapy is indicated, and a repeat 18F-FDG-PET/CT scan will be thought of after three, six, and 12 months to observe and tailor the immunosuppressive remedy (determine 2).
Key messages
Cardiac magnetic resonance tomography with late gadolinium enhancement (CMR-LGE) has a superb detrimental predictive worth to exclude prognostically important cardiac involvement in suspected cardiac sarcoidosis (CS). Nevertheless, CMR-LGE alone can not distinguish between energetic and non-active illness
Positron emission tomography with 18F-fluorodeoxyglucose/computed tomography scan (18F-FDG-PET/CT) is best in detecting the energetic section of CS
18F-FDG-PET/CT is the strategy of alternative to observe and modify immunosuppressive remedy in CS. Serial follow-up at three, six, and 12 months is cheap
18F-FDG-PET/CT needs to be carried out at skilled centres. Correct affected person preparation is important to suppress myocardial glucose uptake and higher visualise 18F-FDG uptake within the affected myocardium
Conflicts of curiosity
None declared.
Funding
None.
Affected person consent
Knowledgeable written affected person consent for publication has been obtained from the affected person described in determine 3.
References
1. Alba AC, Gupta S, Kugathasan L et al. Cardiac sarcoidosis: a scientific overview. Curr Probl Cardiol 2021;46:100936. https://doi.org/10.1016/j.cpcardiol.2021.100936
2. Yazaki Y, Isobe M, Hiroe M et al. Prognostic determinants of long-term survival in Japanese sufferers with cardiac sarcoidosis handled with prednisone. Am J Cardiol 2001;88:1006–10. https://doi.org/10.1016/S0002-9149(01)01978-6
3. Writing group; Doc studying group; EACVI reviewers: this doc was reviewed by members of the EACVI Scientific Paperwork Committee for 2014–2016 and 2016–2018. A joint procedural place assertion on imaging in cardiac sarcoidosis: from the Cardiovascular and Irritation & An infection Committees of the European Affiliation of Nuclear Drugs, the European Affiliation of Cardiovascular Imaging, and the American Society of Nuclear Cardiology. Eur Coronary heart J Cardiovasc Imaging 2017;18:1073–89. https://doi.org/10.1093/ehjci/jex146
4. Schupp JC, Freitag-Wolf S, Bargagli E et al. Phenotypes of organ involvement in sarcoidosis. Eur Respir J 2018;51:1700991. https://doi.org/10.1183/13993003.00991-2017
5. Silverman KJ, Hutchins GM, Bulkley BH. Cardiac sarcoid: a clinicopathologic research of 84 unselected sufferers with systemic sarcoidosis. Circulation 1978;58:1204–11. https://doi.org/10.1161/01.CIR.58.6.1204
6. Mehta D, Lubitz SA, Frankel Z et al. Cardiac involvement in sufferers with sarcoidosis: diagnostic and prognostic worth of outpatient testing. Chest 2008;133:1426–35. https://doi.org/10.1378/chest.07-2784
7. Gilotra N, Okada D, Sharma A, Chrispin J. Administration of cardiac sarcoidosis in 2020. Arrhythm Electrophysiol Rev 2020;9:182–8. https://doi.org/10.15420/aer.2020.09
8. Bennett D, Bargagli E, Refini RM, Rottoli P. New ideas within the pathogenesis of sarcoidosis. Professional Rev Respir Med 2019;13:981–91. https://doi.org/10.1080/17476348.2019.1655401
9. Grunewald J, Grutters JC, Arkema EV, Saketkoo LA, Moller DR, Müller-Quernheim J. Sarcoidosis. Nat Rev Dis Primers 2019;5:45. https://doi.org/10.1038/s41572-019-0096-x
10. Serei VD, Fyfe B. The numerous faces of cardiac sarcoidosis. Am J Clin Pathol 2020;153:294–302. https://doi.org/10.1093/ajcp/aqz169
11. Bagwan IN, Hooper LV, Sheppard MN. Cardiac sarcoidosis and sudden demise. The guts could look regular or mimic different cardiomyopathies. Virchows Arch 2011;458:671–8. https://doi.org/10.1007/s00428-010-1003-8
12. Ribeiro Neto ML, Jellis CL, Joyce E, Callahan TD, Hachamovitch R, Culver DA. Replace in cardiac sarcoidosis. Ann Am Thorac Soc 2019;16:1341–50. https://doi.org/10.1513/AnnalsATS.201902-119CME
13. Roth D, Kadoglou N, Leeflang M, Spijker R, Herkner H, Trivella M. Diagnostic accuracy of cardiac MRI, FDG-PET, and myocardial biopsy for the prognosis of cardiac sarcoidosis: a protocol for a scientific evaluate and meta-analysis. Diagn Progn Res 2020;4:5. https://doi.org/10.1186/s41512-020-00073-4
14. Willy Okay, Dechering DG, Reinke F, Bögeholz N, Frommeyer G, Eckardt L. The ECG in sarcoidosis – a marker of cardiac involvement? Present proof and scientific implications. J Cardiol 2021;77:154–9. https://doi.org/10.1016/j.jjcc.2020.07.006
15. Barssoum Okay, Altibi AM, Rai D et al. Speckle monitoring echocardiography can predict subclinical myocardial involvement in sufferers with sarcoidosis: a meta-analysis. Echocardiography 2020;37:2061–70. https://doi.org/10.1111/echo.14886
16. Narasimhan B, Patel N, Ho Okay et al. Incidence and predictors of sudden cardiac arrest in sarcoidosis: a nationwide evaluation. JACC Clin Electrophysiol 2021;7:1087–95. https://doi.org/10.1016/j.jacep.2021.01.022
17. Handa T, Nagai S, Ueda S et al. Significance of plasma NT-proBNP ranges as a biomarker within the evaluation of cardiac involvement and pulmonary hypertension in sufferers with sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2010;27:27–35. Obtainable from: https://www.researchgate.internet/publication/47814082_Significance_of_plasma_NT-proBNP_levels_as_a_biomarker_in_the_assessment_of_cardiac_involvement_and_pulmonary_hypertension_in_patients_with_sarcoidosis
18. Baba Y, Kubo T, Kitaoka H et al. Usefulness of high-sensitive cardiac troponin T for evaluating the exercise of cardiac sarcoidosis. Int Coronary heart J 2012;53:287–92. https://doi.org/10.1536/ihj.53.287
19. Holtzclaw AW, Mrsic Z, Church TL et al. Optimizing routine screening for cardiac sarcoidosis by means of use of generally out there research. Respir Med 2021;178:106331. https://doi.org/10.1016/j.rmed.2021.106331
20. Crouser ED, Maier LA, Wilson KC et al. Analysis and detection of sarcoidosis. An official American Thoracic Society scientific observe guideline. Am J Respir Crit Care Med 2020;201:e26–e51. https://doi.org/10.1164/rccm.202002-0251ST
21. Chareonthaitawee P, Beanlands RS, Chen W et al. Joint SNMMI-ASNC skilled consensus doc on the position of 18F-FDG PET/CT in cardiac sarcoid detection and remedy monitoring. J Nucl Cardiol 2017;24:1741–58. https://doi.org/10.1007/s12350-017-0978-9
22. Padala SK, Peaslee S, Sidhu MS, Steckman DA, Judson MA. Influence of early initiation of corticosteroid remedy on cardiac operate and rhythm in sufferers with cardiac sarcoidosis. Int J Cardiol 2017;227:565–70. https://doi.org/10.1016/j.ijcard.2016.10.101
23. Smedema JP, Ainslie G, Crijns HJGM. Assessment: contrast-enhanced magnetic resonance within the prognosis and administration of cardiac sarcoidosis. Prog Cardiovasc Dis 2020;63:271–307. https://doi.org/10.1016/j.pcad.2020.03.011
24. Hulten E, Aslam S, Osborne M, Abbasi S, Bittencourt MS, Blankstein R. Cardiac sarcoidosis – cutting-edge evaluate. Cardiovasc Diagn Ther 2016;6:50–63. https://doi.org/10.3978/j.issn.2223-3652.2015.12.13
25. Coleman GC, Shaw PW, Balfour PC Jr et al. Prognostic worth of myocardial scarring on CMR in sufferers with cardiac sarcoidosis. JACC Cardiovasc Imaging 2017;10:411–20. https://doi.org/10.1016/j.jcmg.2016.05.009
26. Mankad P, Mitchell B, Birnie D, Kron J. Cardiac sarcoidosis. Curr Cardiol Rep 2019;21:152. https://doi.org/10.1007/s11886-019-1238-1
27. Zhang J, Li Y, Xu Q, Xu B, Wang H. Cardiac magnetic resonance imaging for prognosis of cardiac sarcoidosis: a meta-analysis. Can Respir J 2018;2018:7457369. https://doi.org/10.1155/2018/7457369
28. Osborne MT, Hulten EA, Murthy VL et al. Affected person preparation for cardiac fluorine-18 fluorodeoxyglucose positron emission tomography imaging of irritation. J Nucl Cardiol 2017;24:86–99. https://doi.org/10.1007/s12350-016-0502-7
29. Birnie DH, Sauer WH, Bogun F et al. HRS skilled consensus assertion on the prognosis and administration of arrhythmias related to cardiac sarcoidosis. Coronary heart Rhythm 2014;11:1305–23. https://doi.org/10.1016/j.hrthm.2014.03.043
30. Kim SJ, Pak Okay, Kim Okay. Diagnostic efficiency of F-18 FDG PET for detection of cardiac sarcoidosis: a scientific evaluate and meta-analysis. J Nucl Cardiol 2020;27:2103–15. https://doi.org/10.1007/s12350-018-01582-y
31. Bhatia Okay, Ramirez R, Narasimhan B et al. Prognostic position of positron emission tomography in sufferers with identified or suspected cardiac sarcoidosis. A scientific evaluate and meta-analysis. Eur Coronary heart J 2020;41(suppl 2):286. https://doi.org/10.1093/ehjci/ehaa946.0286
32. Lee PI, Cheng G, Alavi A. The position of serial FDG PET for assessing therapeutic response in sufferers with cardiac sarcoidosis. J Nucl Cardiol 2017;24:19–28. https://doi.org/10.1007/s12350-016-0682-1
33. Muser D, Santangeli P, Castro SA et al. Prognostic position of serial quantitative analysis of 18F-fluorodeoxyglucose uptake by PET/CT in sufferers with cardiac sarcoidosis presenting with ventricular tachycardia. Eur J Nucl Med Mol Imaging 2018;45:1394–404. https://doi.org/10.1007/s00259-018-4001-8
34. Kersey CB, Flaherty KR, Goldenthal IL, Bokhari S, Biviano AB. The usage of serial cardiac 18F-fluorodeoxyglucose–positron emission tomography imaging to diagnose, monitor, and tailor therapy of cardiac sarcoidosis sufferers with arrhythmias: a case sequence and evaluate. Eur Coronary heart J Case Rep 2019;3:1–7. https://doi.org/10.1093/ehjcr/ytz188
35. Patel AR, Kramer CM. Position of cardiac magnetic resonance within the prognosis and prognosis of nonischemic cardiomyopathy. JACC Cardiovasc Imaging 2017;10:1180–93. https://doi.org/10.1016/j.jcmg.2017.08.005
36. Lemay S, Massot M, Philippon F et al. Ten questions cardiologists ought to be capable to reply about cardiac sarcoidosis: case-based method and up to date evaluate. CJC Open 2021;3:532–48. https://doi.org/10.1016/j.cjco.2020.11.022
37. Kouranos V, Sharma R. Cardiac sarcoidosis: state-of-the-art evaluate. Coronary heart 2021;107:1591–9. https://doi.org/10.1136/heartjnl-2019-316442
38. Tadic M, Cuspidi C, Saeed S, Milojevic B, Milojevic IG. The position of cardiac magnetic resonance in prognosis of cardiac sarcoidosis. Coronary heart Fail Rev 2021;26:653–60. https://doi.org/10.1007/s10741-020-10035-z