Table 1 Inclusion Criteria

Clinical diagnosis of cardiac sarcoidosis according to either the Heart Rhythm Society Diagnostic Criteria [16] based on one of the 2 diagnosis pathways (see below):

 1. Histological diagnosis from myocardial tissue: cardiac sarcoidosis is diagnosed in the presence of non-caseating granuloma on histologic examination of myocardial tissue with no alternative cause identified (including negative stain for microorganisms—as applicable)

 2. Clinical diagnosis from invasive and/or non-invasive studies: it is probable that there is cardiac sarcoidosis if there is (a) histological diagnosis of extracardiac sarcoidosis and (b) one or more of the following: steroid ± immunosuppressant responsive cardiomyopathy or heart block; unexplained reduction in LVEF (< 40%); unexplained sustained (spontaneous or induced) ventricular tachycardia; Mobitz type II 2nd degree or 3rd degree AV block; patchy uptake on dedicated cardiac PET (in a pattern consistent with cardiac sarcoidosis); late gadolinium enhancement on cardiac magnetic resonance (in a pattern consistent with cardiac sarcoidosis); positive gallium uptake (in a pattern consistent with cardiac sarcoidosis) and (c) other causes for the cardiac manifestation(s) have been reasonable excluded

or the diagnostic guidelines for cardiac sarcoidosis based on New CS Guidelines in Japan [17] (see below):

 1. Histological diagnosis group (those with positive myocardial biopsy findings)

Cardiac sarcoidosis is diagnosed histologically when endomyocardial biopsy or surgical specimens demonstrate non-caseating epithelioid granulomas

 2. Clinical diagnosis group (those with negative myocardial biopsy findings or those not undergoing myocardial biopsy)

The patient is clinically diagnosed as having sarcoidosis:

 (1) When epithelioid granulomas are found in organs other than the heart and clinical findings strongly suggestive of the above-mentioned cardiac involvement are present (Table 1A); or

R(2) When the patient shows clinical findings strongly suggestive of pulmonary or ophthalmic sarcoidosis; at least 2 of the 5 characteristic laboratory findings of a sarcoidosis (Table 1B); and clinical findings strongly suggest the above-mentioned cardiac involvement (Table 1A)

Cardiac findings should be assessed based on the major criteria and the minor criteria. Clinical findings that satisfy the following 1) or 2) strongly suggest the presence of cardiac involvement

 1. 2 or more of the 5 major criteria (a)-(e) are satisfied

 2. 1 of the 5 major criteria (a)-(e) and 2 or more of the 3 minor criteria (f)-(h) are satisfied

1. Major criteria:

 a. High-grade AV block (including complete AV block) or fatal ventricular arrhythmia (e.g., sustained VT and VF)

 b. Basal thinning of the ventricular septum or abnormal ventricular wall anatomy (ventricular aneurysm, thinning of the middle or upper ventricular septum, regional wall thickening

 c. Left ventricular contractile dysfunction (LVEF < 50%)

 d. ⁶⁷Ga citrate scintigraphy or ¹⁸F-FDG PET reveals abnormally high tracer accumulation in the heart

 e. Gadolinium-enhanced MRI revealed delayed contrast enhancement of the myocardium

2. Minor criteria

 f. Abnormal ECG findings: Ventricular arrhythmias (nonsustained VT, multifocal or frequent premature ventricular contractions, bundle branch block, axis deviation, or abnormal Q waves

 g. Perfusion defects on myocardial perfusion scintigraphy (SPECT)

 h. Endomyocardial biopsy: Monocyte infiltration and moderate or severe myocardial interstitial fibrosis

1. Bilateral hilar lymphadenopathy

2. High serum angiotensin-converting (ACE) activity or elevated serum lysozyme levels

3. High serum soluble interleukin-2 receptor (sIL-2R) levels

4. Significant tracer accumulation in 67 Ga citrate scintigraphy or 18F-FDG PET

5. A high percentage of lymphocytes with a CD4CD8 ration of > 3.5 in BAL fluid

or the Diagnostic guidelines for isolated cardiac sarcoidosis based on New CS Guidelines in Japan [17]

Diagnostic guidelines for isolated cardiac sarcoidosis

Prerequisites

1. No clinical findings characteristic of sarcoidosis are observed in any organs other than the heart. (The patient should be examined in detail for respiratory, ophthalmic, and skin involvement of sarcoidosis. When the patient is symptomatic, other etiologies that can affect the corresponding organs must be ruled out.)

2. ⁶⁷Ga scintigraphy or ¹⁸F-FDG PET reveals no abnormal tracer accumulation in any organs other than the heart

3. A chest CT scan reveals no shadow along the lymphatic tracts in the lungs or no hilar and mediastinal lymphadenopathy (minor axis > 10 mm)

(1) Histological diagnosis group

Isolated cardiac sarcoidosis is diagnosed histologically when endomyocardial biopsy or surgical specimens demonstrate non-caseating epithelioid granulomas

(2) Clinical diagnosis group

Isolated cardiac sarcoidosis is diagnosed clinically when criterion (d) and at least 3 other major criteria (a)-(e) are satisfied. (Table 1A)

2. Cardiac fluoro-deoxyglucose uptake on recent PET (performed within the prior 60 days)

3. CRP high-sensitivity assay ≥ 2 mg/l (performed within the prior 60 days)