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Reviews in Cardiovascular Medicine  2020, Vol. 21 Issue (3): 321-338     DOI: 10.31083/j.rcm.2020.03.102
Special Issue: Cardiac fibrosis
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Cardiac sarcoidosis: diagnosis and management
Eleftherios Markatis1, *(), Andreas Afthinos1, Emmanouil Antonakis1, Ilias C Papanikolaou1, *()
1Pulmonary Department, Corfu General Hospital, Corfu 49100, Greece
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Sarcoidosis is a chronic inflammatory disease of unknown etiology characterized by multi-organ involvement. End-organ disease consists of granulomatous inflammation, which if left untreated or not resolved spontaneously, leads to permanent fibrosis and end-organ dysfunction. Cardiac involvement and fibrosis in sarcoidosis occur in 5-10% of cases and is becoming increasingly diagnosed. This is due to increased clinical awareness among clinicians and new diagnostic modalities, since magnetic resonance imaging and positron-emission tomography are emerging as “gold standard” tools replacing endomyocardial biopsy. Despite this progress, isolated cardiac sarcoidosis is difficult to differentiate from other causes of arrhythmogenic cardiomyopathy. Cardiac fibrosis leads to congestive heart failure, arrhythmias and sudden cardiac death. Immunosuppressives (mostly corticosteroids) are used for the treatment of cardiac sarcoidosis. Implantable devices like a cardioverter-defibrillator may be warranted in order to prevent sudden cardiac death. In this article current trends in the pathophysiology, diagnosis and management of cardiac sarcoidosis will be reviewed focusing on published research and latest guidelines. Lastly, a management algorithm is proposed.

Key words:  Sarcoidosis      cardiac sarcoidosis      interstitial lung disease      fibrosis     
Submitted:  22 May 2020      Revised:  16 August 2020      Accepted:  18 August 2020      Published:  30 September 2020     
*Corresponding Author(s):  Eleftherios Markatis Email:; Ilias C Papanikolaou Email:   

Cite this article: 

Eleftherios Markatis, Andreas Afthinos, Emmanouil Antonakis, Ilias C Papanikolaou. Cardiac sarcoidosis: diagnosis and management. Reviews in Cardiovascular Medicine, 2020, 21(3): 321-338.

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Fig. 1.   A well-formed non-necrotizing granuloma in the heart (Hematoxylin Eosin x400).

Fig. 2.   Cardiac magnetic resonance images in a 54-year-old male with cardiac sarcoidosis, showing late gadolinium enhancement in the posterior-lateral left ventricle wall sub-epicardially (B, yellow arrows).

Table 1.  Japanese cardiac sarcoidosis and Heart Rhythm Society guidelines (Birnie et al., 2014; Terasaki et al., 2019).
2016 JCS Guideline on Diagnosis and Treatment of Cardiac Sarcoidosis 2014 HRS expert consensus statement on the diagnosis and management of arrhythmias associated with cardiac sarcoidosis
• Histological diagnosis • Histological diagnosis
• Clinical diagnosis group when
A. Epithelioid granulomas are found in organs other than the heart, and two or more major criteria or one major and two or more minor criteria • Clinical diagnosis of cardiac sarcoidosis (probable CS) meaning histological diagnosis of extra cardiac sarcoidosis, exclusion of other diagnoses and one or more of
Major criteria
1. High-grade atrioventricular block (including complete atrioventricular block) or fatal ventricular arrhythmia (e.g., sustained ventricular tachycardia, and ventricular fibrillation) 1. cardiomyopathy and/or heart block unexplained reduced left ventricular ejection fraction (LVEF) of less than 40%
2. Basal thinning of the ventricular septum or abnormal ventricular wall anatomy (ventricular aneurysm, thinning of the middle or upper ventricular septum, regional ventricular wall thickening) 2. unexplained sustained (spontaneous or induced) ventricular tachycardia
3. Left ventricular contractile dysfunction (left ventricular ejection fraction less than 50%) or focal ventricular wall asynergy
4. 67Ga citrate scintigraphy or FDG PET reveals abnormally high tracer accumulation in the heart 3. Mobitz type II second-degree AV block or third-degree AV block
5. Gadolinium-enhanced MRI reveals delayed contrast enhancement of the myocardium
Minor criteria
1. Abnormal ECG findings: Ventricular arrhythmias (nonsustained ventricular tachycardia, multifocal or frequent premature ventricular contractions), bundle branch block, axis deviation, or abnormal Q waves 4. patchy uptake of cardiac FDG-PET in a pattern consistent with cardiac sarcoidosis
2. Perfusion defects on myocardial perfusion scintigraphy (SPECT) 5. late gadolinium enhancement on CMRI in a pattern consistent with cardiac sarcoidosis
3. Endomyocardial biopsy: Monocyte infiltration and moderate or severe myocardial interstitial fibrosis
4. When the patient shows clinical findings strongly suggestive of pulmonary or ophthalmic sarcoidosis; at least 2 of the five characteristic laboratory findings of sarcoidosis and clinical findings strongly suggest cardiac involvement 6. positive gallium uptake in a pattern consistent with cardiac sarcoidosis
Table 2.  Probable cardiac sarcoidosis according to World Association of Sarcoidosis and Other Granulomatous diseases (WASOG) criteria (Crouser et al., 2020; Judson et al., 2014).
2014 The WASOG Sarcoidosis Organ Assessment Instrument 2020 Diagnosis and Detection of SarcoidosisAn Official American Thoracic Society Clinical Practice Guideline
Probable criteria Probable criteria
1. Treatment responsive Cardiomyopathy or atrioventricular nodal block 1. Treatment-responsive CM or AVNB
2. Reduced LVEF in the absence of other clinical risk factors 2. Reduced LVEF with no risk factors (echo and MRI)
3. Spontaneous or inducible sustained VT with no other risk factor 3. Spontaneous/inducible VT with no risk factors
4. Mobitz type II or 3rd degree heart block 4. New-onset, third-degree AV block in young or middle-aged adults
5. Patchy uptake on dedicated cardiac PET 5. Increased inflammatory activity in heart (MRI, PET, and gallium)
6. Delayed enhancement on CMR
7. Positive gallium uptake
8. Defect on perfusion scintigraphy or SPECT scan
9. T2 prolongation on CMR
(FDG) PET = (Fluorodeoxyglucose) positron emission tomography; MRI = magnetic resonance imaging; ECG = electrocardiogram; SPECT = Single-photon emission computed tomography; LVEF = left ventricular ejection fraction; VT = ventricular tachycardia; CM = cardiomyopathy; AVNB = atrioventricular node block; AV = atrioventricular
Fig. 3.  FDG-PET of a 63-year-old female on methotrexate for cardiac sarcoidosis before (a) and during (b) therapy with methotrexate for 2 years, exhibiting a significant decrease in FDG uptake in the heart suggesting adequate response to therapy. The scan continues to show FDG uptake in mediastinal lymph nodes (Bremer et al., 2018)

Table 3.  Studies on cardiac sarcoidosis treatment.
Authors Number of patients Year of study High dose Immunosuppresion Tapering Low dose Immunosuppresion
Yazaki et al., 2001 95 2001 Prednisone 30-60 mg/d Variable Prednisone 5 to 15 mg/d
Chapelon-Abric et al., 2004 41 2004 IV prednisolone 15mg/kg × 3d Variable Not reported
Chiu et al., 2005 43 2005 Prednisone 60 mg 2 months Prednisone 10 mg/ d
Nagai et al., 2014 17, 67 2014, 2015 Prednisone 30 to 40 mg/d Variable Prednisolone 5 to 15 mg/d
Ballul et al., 2019 36 2016 Prednisone 60 mg/d Not reported Not reported
Fussner et al., 2018 91 2018 Prednisone 40-60 mg/d Variable Variable
Fig. 4.  Suggested management algorithm for patients with probable cardiac sarcoidosis. ATS, American thoracic society criteria, biopsy of extra cardiac site; ECG, electrocardiogram; CMR, cardiac magnetic resonance, PET, positron emission tomography; VA, ventricular arrythmias; LVEF, left ventricle ejection fraction; EPS, electrophysiologic study; ICD, implantable cardioverter defibrillator.

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