Download Cardiac Sarcoidosis

Cardiac
Sarcoidosis
Millee Singh DO
Non Invasive Cardiology
First Coast Heart and
Vascular
Introduction
 Multisystem
granulomatous disease of
unknown etiology characterized by noncaseating 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: 546-554
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 20- 30%
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%
Sekhri et al. Arch Med Sci 2011; 7, 4: 546-554
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
Pathophysiology
Three aspects :
1. Exposure to antigen
2. Acquired cellular immunity directed against
the antigen mediated through antigen
presenting cells and antigen specific T
lymphocytes
3. Appearance of immune effector cells that
promote a more nonspecific inflammatory
response
ALL LEADING TO GRANULOMA FORMATION
AND PROGRESSION TO FIBROSIS OF TISSUE

Sekhri et al. Arch Med Sci 2011; 7, 4: 546-554
Arch Med Sci 4, August / 2011
Pathology



1.
2.
3.
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: 86-108
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
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

Clinical Presentation/Diagnosis
Sekhri et al. Arch Med Sci 2011; 7, 4: 546-554
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: 54-
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 - 23-30%
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/presyncope should be evaluated for CHB
Yoshida et al. Am Heart J 1997; 134: 382-6.
Ventricular arrhythmias
 Sudden
death caused by ventricular
tachyarrhythmia's may account for 2565% 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: 249-63.
Congestive Heart Failure
 Accounts
for 25% to 75% of cardiac
deaths in patients with cardiac sarcoidosis
 Heart failure may be secondary to leftsided 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: 1006-10.
Other Cardiac Manifestations
 Pericardial

< 10 % of Cases- Small in size
 Valvular

Involvement
< 3 % , mostly Mitral Regurgitation noted
 Ventricular



Effusions
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
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
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
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: 546-554
Imaging

Doppler echocardiography




Radionuclide studies


Abnormal septal thickening or thinning
Dilatation of the left ventricle
Systolic dysfunction of the left ventricle
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: 465-71
.Haywood et al; J Natl Med Assoc 1983; 63: 478-82
Fields et al. ; South Med J 1990; 83: 339-42
Imaging- CMR


Technique of choice in the evaluation of
sarcoidosis
zone of increased intramyocardial signal
intensity



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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: 110-5.
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: 143-6.
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: 143-6.
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
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: 244-50.
KEY POINTS


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

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