Table 1
Features of cardiac sarcoidosis as shown on 18fluorine-fluorodeoxyglucose-postrion emission tomography. Adapted from Blankstein et al. J Am Coll Cardiol. 2014.33 FDG: 18fluorine-fluorodeoxyglucose
| FDG UPTAKE | REST PERFUSION | INTERPRETATION |
|---|---|---|
| Normal metabolism and perfusion | ||
| None | Normal | Normal study |
| Diffuse uptake (nonspecific) | Normal | Inadequate myocardial glucose suppression |
| Abnormal metabolism or perfusion | ||
| Focal uptake | Normal | Early disease or normal variant |
| None | Perfusion defect | Scar from any etiology |
| Abnormal metabolism and perfusion | ||
| Focal uptake | Perfusion defect in area of focal FDG uptake | Inflammation + scar in the same area |
| Focal uptake | Perfusion defect in area separate from FDG uptake | Inflammation + scar in different areas |
| Focal on diffuse uptake | Multiple perfusion defects | Diffuse inflammation or inflammation + inadequate glucose suppression and scar |
Figure 1
Diagnosis of cardiac sarcoidosis. LV: left ventricular; CMR: cardiac magnetic resonance; LGE: late gadolinium enhancement; FDG-PET: fluorine-fluorodeoxyglucose-positron emission tomography
Table 2
Summary of Heart Rhythm Society and Japanese Circulation Society guidelines for diagnosis of CS. CS: cardiac sarcoidosis; LVEF: left ventricular ejection fraction: VT: ventricular tachycardia; VF: ventricular fibrillation; PET: positron emission tomography; CMR: cardiac magnetic resonance; 18F-FDG-PET: 18fluorine-fluorodeoxyglucose-postrion emission tomography; EKG: echocardiographic Adapted from3,35,42
| HEART RHYTHM SOCIETY GUIDELINES | JAPANESE CIRCULATION SOCIETY GUIDELINES |
|---|---|
| Definite or histological diagnosis: Requires presence of noncaseating granulomas myocardial tissue and absence of alternative cause A. Probable* or clinical diagnosis: Histological diagnosis of extracardiac sarcoidosis AND Presence of ≥ 1 of the following:
AND B. Other causes for the cardiac manifestation(s) have been reasonably excluded *Probable is considered adequate to establish a clinical diagnosis of CS | 1) Histological diagnosis group: Requires biopsy findings demonstrating noncaseating epithelioid granulomas from endomyocardial biopsy or surgical cardiac specimens 2) Clinical diagnosis group: (negative myocardial biopsy or not undergoing myocardial biopsy) A) Extracardiac biopsy proven sarcoid AND clinical findings strongly suggestive of cardiac involvement** OR B) Clinical findings strongly suggestive of pulmonary or ophthalmic sarcoid AND At least 2 out of 5 characteristic lab findings of sarcoidosis*** AND Clinical findings strongly suggestive of cardiac involvement** |
| **Clinical findings defining cardiac involvement 1) Two or more of the five major criteria (a) to (e) are satisfied 2) One of the five major criteria (a) to (e) and two or more of the three minor criteria (f) to (h) are satisfied | |
| Criteria for cardiac involvement of sarcoidosis 1. Major criteria (a) High-grade atrioventricular block or VT/VF (b) 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) (c) Left ventricular contractile dysfunction (LVEF < 50%) (d) 67Ga citrate scintigraphy or 18F-18FDG-PET reveals abnormally high tracer accumulation in the heart (e) Gadolinium-enhanced MRI reveals delayed contrast enhancement of the myocardium 2. Minor criteria (f) Abnormal EKG findings: ventricular arrhythmias (nonsustained ventricular tachycardia, multifocal or frequent premature ventricular contractions), bundle branch block, axis deviation, or abnormal Q waves (g) Perfusion defects on myocardial perfusion scintigraphy (h) Endomyocardial biopsy: monocyte infiltration and moderate or severe myocardial interstitial fibrosis |
[i] *** Clinical diagnosis of sarcoidosis is supported when at least two of the five characteristic findings are observed.
Bilateral hilar lymphadenopathy
High serum angiotensin-converting enzyme activity or elevated serum lysozyme levels
High serum soluble interleukin-2 receptor levels
Significant tracer accumulation in 67Ga citrate scintigraphy or 18FDG-PET
A high percentage of lymphocytes with a CD4/CD8 ratio of > 3.5 in BAL fluid
Table 3
| PREREQUISITE CRITERIA | |
|---|---|
| 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 involvements of sarcoidosis. When the patient is symptomatic, other etiologies that can affect the corresponding organs must be ruled out.) 2. 67Ga scintigraphy or 18FDG-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). | |
| CLINICAL DIAGNOSIS GROUP | HISTOLOGICAL DIAGNOSIS GROUP |
| Prerequisite criteria AND ≥ three other criteria of the major criteria (a)-(e) are satisfied per JCS guidelines, Table 2* | Demonstration of noncaseating epithelioid granulomas in endomyocardial biopsy or surgical specimens |
[i] 18FDG-PET: 18fluorine fluorodeoxyglucose-positron emission tomography; CT: computed tomography
* Refer JCS guidelines in Table 2 for major criteria a-e
Table 4
Prevalence of isolated cardiac sarcoidosis.71,72,73,74,75,76,77 AV block: atrioventricular block; CMR: cardiac magnetic resonance; PET: positron emission tomography; EMB: endomyocardial biopsy; HF: heart failure; HRS: Heart Rhythm Society; JHMW: JHM strain of mouse hepatitis virus; LN: lymph node; VA: ventricular arrhythmias; VF: ventricular fibrillation; VT: ventricular tachycardia; 18FDG-PET: 18fluorine-fluorodeoxyglucose PET; WASOG: World Association for Sarcoidosis and Other Granulomatous Diseases
| AUTHOR | STUDY PERIOD | N | STUDY POPULATION | COUNTRY | STUDY POPULATION CLINICAL MANIFESTATIONS N (%) | DIAGNOSTIC MODALITIES (N) | PREVALENCE n (%) | MEDIAN AGE | SEX MALE |
|---|---|---|---|---|---|---|---|---|---|
| Kandolin et al. | 1998–2014 | 110 | Patients diagnosed with CS | Finland | AV block 48 (44) VT/VF 36 (33) HF 20 (18) | EMB (55/92) Explant (6) Autopsy (2) mediastinal LN biopsy (18) Whole body PET 31 CMR 59 PET 66 CMR and/or PET (38) Other (9) | Definite: 59/110 (54) | 51 ± 9 | 39 |
| Tezuka et al. | 1995–2008 | 83 | Patients with clinical sarcoidosis | Japan | N = 15 VA 8 (53)VT 7 (47)VF 1 (7)Automatic ICD 9 (60)Complete AV block 3 (20) HF 6 (40) | JCS Criteria CMR FDG-PET EMB | Definite: 11/41 (27) | 63.5 ± 15.9* | 7* |
| Simonen et al. | 2005–2013 | 68 | Patients with known CS | Finland | Complete AV block 37 (54) Sustained VT 18 (26) HF 7 (10) VF 4 (6) PVCs 2 (2.3) | Cardiac 18FDG PET (68) CMR (43) EMB (56) Whole body 18FDG PET (n = 57) Mediastinal LN biopsy (24) | Definite: 13/57 (23) | 50 ± 9 | 21 |
| Juneau et al. | 2017 | 31 | Patients first presenting with clinically manifest CS | Canada | High-degree AV block 18 (58) VT or cardiac arrest 6 (19) High-degree AB block/VT 3 (10) HF 3 (10) Other 1 (3) | Cardiac and whole body 18FDG-PET-CT | Definite: 1/31 (3.2) | 56 ± 8 | 14 |
| Giudicatti et al. | 2007–2018 | 52 | All cases of proven or probable CS based on HRS and local consensus | Australia | HF 17 (53) VF/VT 7 (22) ICD 21 (66) | Cardiac and whole body 18FDG-PET-CT | Definite: 3/32 (9.4) | 59 | 22 |
| Kawai H | 2013–2019 | 94 | All patients with suspected CS | Japan | N = 7* Sustained VT/VF or high-degree conduction block 4 (57) HF 7 (100) | Cardiac and whole body 18FDG-PET-CT | Clinical: 7/34 (21) Based on JCS guidelines | 59.4 ± 14.9* | 4* |
| Sperry BW | 2002–2014 | 27 | EMB-proven CS | USA | High-degree AV block 15 (56) HF 27 (100) VT 16 (59) | 18FDG-PET-CT (16) CMR (12) | Definite: 14/27 (52) | 53.8 ± 9.5 | 16 |
| Chazal et al. | 2000–2017 | 15 | CS in explanted hearts/ATS- or WASOG-based diagnosis of sarcoidosis | France | VT 7 (47) VF 1 (7) Complete AV block 3 (20) HF 6 (40) | Echocardiography CMR (6) FDG-PET (2) | Definite: 3/15 (20) | 48 | 10 |
[i] * In iCS group.
Table 5
| DISEASE | CLINICAL FEATURES | HISTOLOGY | IMAGING |
|---|---|---|---|
| Giant cell myocarditis | Ventricular arrhythmias Complete heart block Rapidly progressive heart failure, shock | Lack of granuloma formation Inflammatory infiltrate of eosinophils, lymphocytes, macrophages, and giant cells associated with myocyte necrosis | Echocardiographic findings: wall thickening, normal or enlarged LV size, decreased LV systolic function with acute progression to LV dilation and decreased LVEF |
| Idiopathic dilated cardiomyopathy | Heart failure, arrhythmia Positive family history | Myocyte hypertrophy and replacement fibrosis with variable involvement of the conduction system | Dilated LV with global ventricular dysfunction Linear stripe of LGE in ventricular septum on MRI or no LGE |
| Arrhythmogenic RV cardiomyopathy | Ventricular arrhythmias RV failure Family history Sudden cardiac death | Transmural fibrofatty replacement of myocardium | RV dilatation and dysfunction Fibrofatty infiltration of RV Dyskinesia of RV free wall with RV aneurysms |
| Amyloidosis | Heart failure Heart block Atrial fibrillation Multiple myeloma, renal insufficiency and/or nephrotic syndrome | Amorphous hyaline deposits seen predominantly in the extracellular space Typical apple-green birefringence with Congo red dye under polarized light microscopy and unique cross–β-pleated sheets under electron microscopy | Biventricular hypertrophy including valves and RV Biatrial enlargement Diffuse nulling abnormality of myocardium on MRI with LGE |
| Hypertrophic cardiomyopathy | Heart failure Ventricular arrhythmias Atrial fibrillation Family history | Myocyte hypertrophy and disarray Presence of interstitial and replacement fibrosis | LV hypertrophy > 15 mm (often asymmetric) Scattered patchy midmyocardial scar on MRI and LGE predominant in RV insertion points of ventricular septum |
| Myocarditis (tuberculous, fungal, bacterial, viral) | Heart failure Chest pain Atrial and ventricular arrhythmias Clinical features of causative organism | Necrotizing granulomas in case of TB, disseminated fungal infection Demonstration of implicated organisms on staining Myofiber necrosis Neutrophilic or mononuclear infiltrate Chronic stages: fibrosis with disruption of the normal myocardial architecture | Patchy epicardial LGE Edema on MRI |
[i] LV: left ventricular; LVEF: LV ejection fraction; LGE: late gadolinium enhancement; MRI: magnetic resonance imaging; RV: right ventricular
Figure 2
Approach to diagnosis for suspected cardiac sarcoidosis. LVEF: left ventricular ejection fraction; MRI: magnetic resonance imaging; 18FDG-PET: 18fluorine-fluorodeoxyglucose postrion emission tomography; PET: positron emission tomography; ICD: implantable cardioverter defibrillator
Figure 3
Approach to screening for patients with extracardiac sarcoidosis. AV: atrioventricular; RBBB: right bundle branch block; LVEF: left ventricular ejection fraction; RWMA: regional wall motion abnormalities; MRI: magnetic resonance imaging; 18FDG-PET: 18fluorine-fluorodeoxyglucose postrion emission tomography; PET: positron emission tomography; ICD: implantable cardioverter defibrillator; EP: electrophysiological; EKG: electrocardiogram: echo: echocardiogram