1. Millee Singh DO Non Invasive Cardiology First Coast Heart and Vascular
Cardiac Sarcoidosis
Millee Singh DO
Non Invasive Cardiology
First Coast Heart and Vascular

2. Introduction
Multisystem granulomatous disease of unknown etiology characterized by non-caseating granulomas in involved organs
The prevalence is 10-40/100,000 persons in the United States and Europe
Increased prevalence in African- Americans compared to Caucasians with a ratio ranging from 17 : 1
Sekhri et al. Arch Med Sci 2011; 7, 4:

3. Introduction Sarcoidosis is more prevalent in women than in men
Organs involved Include :
Lymph nodes, skin, lung, central nervous system, and eye
Cardiac involvement in sarcoidosis occurs in % of patients in reported pathology series
A review of 84 autopsy cases of pulmonary sarcoidosis and found myocardial granulomas in 27% of patients
In Sarcoidosis, deaths from Cardiac sarcoid appear to have a regional connection :
United States, 13 to 25%
Japan, 47 to 85%
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4. Introduction Genetic link:
A Case Controlled Etiologic Sarcoidosis Study (ACCESS) concluded that first-degree relatives of patients with sarcoidosis had a relative risk of sarcoidosis that was five times that of control subjects

5. Pathophysiology Three aspects : Exposure to antigen
Acquired cellular immunity directed against the antigen mediated through antigen presenting cells and antigen specific T lymphocytes
Appearance of immune effector cells that promote a more nonspecific inflammatory response
ALL LEADING TO GRANULOMA FORMATION AND PROGRESSION TO FIBROSIS OF TISSUE
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6. Arch Med Sci 4, August / 2011

7. Pathology
Characteristic lesion of sarcoidosis is a discrete, compact, noncaseating epitheloid cell granuloma
Cardiac sarcoidosis is associated with noncaseating granulomas which may involve the left ventricular free wall, basal ventricular septum, right ventricle, papillary muscles, right atrium, and left atrium
3 successive histological stages:
Edema
Granulomatous infiltration
Fibrosis leading to post- inflammatory scarring
Roberts et al. ;Am J Med 1977; 63:

8. Pathology Pathological slides:
Myocardium show the presence of numerous lymphocytes located at the border zones around the granulomas
A dense band of fibroblasts, collagen fibers, and pro- teoglycans usually encase this aggregate of inflammatory cells

9. Clinical Presensation/Diagnosis
Symptoms which include fever, fatigue, malaise, and weight loss can be very vague presentation overall
When multi-systemic sarcoidosis has already been diagnosed – Cardiac diagnosis of symptoms are easier to diagnosed
When cardiac dysfunction is the only manifestation of sarcoidosis, the diagnosis is frequently not entertained

10. Clinical Presentation/Diagnosis
Sekhri et al. Arch Med Sci 2011; 7, 4:

11. Clinical Presentation/Diagnosis
Early diagnosis and treatment is essential since treatment improves prognosis
Serious cardiac dysfunction is detected in 5% to 10% of cases
In a significant proportion of patients with cardiac sarcoidosis, the initial presentation is sudden death
Sarcoid granulomas may serve as foci for abnormal automaticity or reentrant tachycardias
Atrial arrhythmias are less common
15-17% of cases
Result of atrial dilatation or pulmonary involvement rather than the result of atrial granulomas
Fleming HA. Sarcoid heart disease. Br Heart J 1974; 36:

12. Complete Heart Block
Occurs in younger age in patients with sarcoidosis than in patients with complete heart block of other causes
Rate of occurrence :
Complete heart block %
Bundle branch block 12-32%
Caused by the involvement of basal septum by scar tissue, granulomas, or involvement of the nodal artery causing ischemia in the conduction system
Sarcoidosis pts who present with syncope/pre- syncope should be evaluated for CHB
Yoshida et al. Am Heart J 1997; 134:

13. Ventricular arrhythmias
Sudden death caused by ventricular tachyarrhythmia's may account for 25-65% of deaths caused by cardiac sarcoidosis
May be the initial presentation in 40% of patients with cardiac sarcoidosis
Sekiguchi et al. I Sarcoidosis. Jpn Circ J 1980; 44:

14. Congestive Heart Failure
Accounts for 25% to 75% of cardiac deaths in patients with cardiac sarcoidosis
Heart failure may be secondary to left- sided cardiac involvement with either systolic or diastolic dysfunction
DDx: Idiopathic dilated cardiomyopathy (IDC) can be difficult to differentiate
Sarcoidosis HF tend to have more progression to CHB then IDC
Yazaki et al. Am J Cardiol 2001; 88:

15. Other Cardiac Manifestations
Pericardial Effusions
< 10 % of Cases- Small in size
Valvular Involvement
< 3 % , mostly Mitral Regurgitation noted
Ventricular Aneurysms
10% of cases
Anterior and septal segments
Usually associated with steroid treatment for sarcoid rather than a direct cause
Garrett et al; Am Heart J 1984; 107: 394
Pesola et a; Sarcoidosis 1987; 4: 42-4

16. Diagnosis
Thorough clinical evaluation documenting a syndrome consistent with sarcoidosis AND Biopsy documentation of the presence of non- caseating granulomas
Uemura et al. ;Am Heart J 1999; 138:299

17. Endomyocardial Biopsy
“ Gold standard”
Definite diagnosis of cardiac sarcoidosis can be made
The sensitivity IS LOW-usually less than 20%
Despite its low sensitivity, early myocardial biopsy can be considered when the diagnosis of cardiac sarcoidosis is still used
Uemura et al. ;Am Heart J 1999; 138:299

18. DDX- Differential Diagnosis
Connective tissue diseases
Lyme disease
Rheumatoid arthritis
Dermatomyositis
Cardiac amyloidosis
alcohol related cardiomyopathy
Sekhri et al. Arch Med Sci 2011; 7, 4:

19. Imaging Doppler echocardiography Radionuclide studies PET
Abnormal septal thickening or thinning
Dilatation of the left ventricle
Systolic dysfunction of the left ventricle
Radionuclide studies
fibrogranulomatous lesions in the myocardium display segmental areas of decreased uptake in nuclear imaging
PET
18F-Fluorodeoxyglucose (FDG) PET appears to detect active cardiac sarcoidosis with high sensitivity
Non-specific for sarcoidosis, and uptake of 18F-FDG is seen in other inflammatory myocardial diseases
Skold et al. J Intern Med 2002; 252:
.Haywood et al; J Natl Med Assoc 1983; 63:
Fields et al. ; South Med J 1990; 83:

20. Imaging- CMR Technique of choice in the evaluation of sarcoidosis
zone of increased intramyocardial signal intensity
More pronounced on T2 weighted images because of edema
These images can be enhanced on gadolinium
Focal myocardial thickening is often seen as a result of the edema
Delayed enhanced MRI is considered a useful method for the early identification of cardiac sarcoidosis
Tadamura et al. AJR Am J Roentgenol 2005; 185:

21. Treatment and Prognosis
Threshold for treatment is lower because of increased risk of sudden death
Goal is to reduce inflammation
Corticosteroids, the most common initial therapy
Should be started in patients with a definite probability of cardiac sarcoidosis on different imaging studies, even with a negative myocardial biopsy
Chiu et al. Am J Cardiol 2005; 95:

22. Treatment Clinical Trials have suggested that Steroid treatments:
(LVEF) > 55% may prevent LV remodeling and altered cardiac function
Most benefited with LVEF < 54% who showed significant reduction in LV volumes and LVEF improvement
LVEF < 30%, steroid therapy did not improve the LV volume or function
Early/Middle stage disease, steroid therapy may be protective or therapeutic but may not be as effective in the late stages
Chiu et al. Am J Cardiol 2005; 95:

23. Other Treatment Options
Methotrexate, azathioprine, or cyclophosphamide can be used as steroid sparing agents and in those whose disease is refractory to high-dose steroids
Improvement in cardiac conduction abnormalities have been seen with the use of infliximab, a TNF alpha inhibitor
Avoid using :
Anti Arrhythmic drugs- Increased SCD
Beta Blockers – Increased Heart Block
ICD implantation in Cardiac sarcoid does have a lower threshold then other Heart Failure guidelines
Baughman et al. Sarcoidosis Vasc Diffuse Lung Dis 2001; 18:70-4
Lower et al . Am J Med Sci 1990; 299: 153-7
Baughman et al. Sarcoidosis Vasc Diffuse Lung Dis 2000; 17: 60-6

24. Cardiac Transplantation
Cardiac transplantation is reserved for end-stage disease unresponsive to medical therapy
Major indications for cardiac transplantation :
Resistant ventricular tachyarrhythmia
Severe intractable heart failure ( Stage D)
Valantine et al. J Heart Transplant 1987; 6:

25. KEY POINTS
Cardiac sarcoidosis may occur alone or alongside systemic sarcoidosis but is frequently clinically silent
Diagnosis is still a major clinical challenges
CMR and PET may be suggestive but are not diagnostic
Endo-myocardial biopsy lacks sensitivity but still is “ Gold Standard”
There is no clear-cut consensus on which diagnostic methodologies are best to evaluate disease presence and progression
Suspect cardiac sarcoidosis in young adults with unexplained cardiac clinical manifestations , with a histologic (or clinical) diagnosis of extra-cardiac sarcoidosis, particularly in those who develop arrhythmias, conduction disease, or heart failure