cor et vasa 60 (2018) e155–e164

Available online at www.sciencedirect.com

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journal homepage: http://www.elsevier.com/locate/crvasa

Review article

Management of cardiac sarcoidosis –

A practical guide

Petr Kopriva a,*, Martin Griva a,b, Zbynek Tüdös c

a
Department of Cardiology, Tomas Bata Regional Hospital, Zlin, Czech Republic
b
Department of Internal Medicine I – Cardiology, Faculty of Medicine and Dentistry, Palacky University Olomouc,
University Hospital Olomouc, Czech Republic
c
Department of Radiology, Faculty of Medicine and Dentistry, Palacky University Olomouc, University Hospital
Olomouc, Czech Republic

article info abstract

Article history: Sarcoidosis is a multi-system granulomatous disorder of unclear etiology which can affect
Received 7 March 2017 any organ of the body including the heart. The heart is involved in up to 25% of sarcoidosis
Received in revised form patients. In rare cases, the heart can be the only organ involved.
17 May 2017 Involvement of the heart, called cardiac sarcoidosis, especially if symptomatic, signifi-
Accepted 20 May 2017 cantly deteriorates the prognosis for sarcoidosis patients, which is why cardiac sarcoidosis
Available online 23 June 2017 should be not only considered, but also searched for actively. Despite recent advances in this
field, diagnosis, risk-stratification, and treatment of cardiac sarcoidosis remains a challeng-
Keywords: ing issue. Fortunately, several recommendations have been recently formulated which
Cardiac magnetic resonance provide relatively clear guidance on the management of patients with cardiac sarcoidosis.
Cardiac sarcoidosis The cornerstone of management of these patients is a multidisciplinary approach involving
Diagnosis collaboration of cardiologists, pulmonologists, radiologists, rheumatologists, and other
Heart failure specialists.
Implantable cardioverter- Currently, diagnosis of cardiac sarcoidosis is based on an assessment of a patients'
defibrilator symptoms, physical examination and results of standard ECG, Holter monitoring and
Positron emission tomography echocardiography. This series of examinations can identify individuals with possible cardiac
Sudden cardiac death sarcoidosis, who should undergo, as the next step, cardiac magnetic resonance and positron
Treatment emission tomography, which are the techniques of choice for the diagnosis of cardiac
sarcoidosis. Histological verification, critical for establishing a definitive diagnosis, is based
– in cases with a typical picture documented by imaging techniques – on an extracardiac
biopsy. In some cases, when an extracardiac biopsy is not feasible, an endomyocardial
biopsy is needed.
The cornerstone of treatment remains corticosteroids, in some cases in combination
with other immunosuppressives, although data on their efficacy and safety from random-
ized trials are lacking. As the most frequent causes of death from cardiac sarcoidosis are
heart rhythm disorders, be it atrioventricular blocks or ventricular arrhythmias, an irre-
placeable role in the management of these patients is played by implantation of pacemakers
and implantable cardioverter/defibrillators (ICD). One of the most critical issues is risk
stratification of patients who, while not meeting classic criteria for ICD implantation,

* Corresponding author.
E-mail address: petr.kopriva@bnzlin.cz (P. Kopriva).
http://dx.doi.org/10.1016/j.crvasa.2017.05.012
0010-8650/© 2017 The Czech Society of Cardiology. Published by Elsevier Sp. z o.o. All rights reserved.
e156 cor et vasa 60 (2018) e155–e164

continue to be at high risk of sudden cardiac death and therefore should still be considered
for ICD implantation. The last option for patients with advanced sarcoidosis is heart
transplantation.
The present paper is an overview of presentation, diagnosis, and treatment of cardiac
sarcoidosis, with special emphasis on the use of algorithms applicable in routine clinical
practice.
© 2017 The Czech Society of Cardiology. Published by Elsevier Sp. z o.o. All rights reserved.

Contents

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e156
Sarcoidosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e156
Cardiac sarcoidosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e156
Clinical manifestations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e156
Diagnosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e157
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e160
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e162
Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e162
Ethical statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e162
Funding body . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e162
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e162

Introduction systemic sarcoidosis [9,10]. However some pathological stud-

ies have suggested some involvement of the heart is present in
Sarcoidosis up to 25% of patients with sarcoidosis [11]. Very rarely, the
heart can be the only organ affected. Involvement of the heart
Sarcoidosis is a multi-system granulomatous disorder of in sarcoidosis patients suggests a less favorable prognosis [12].
unclear etiology which can affect any organ within the body. The strongest prognostic marker is left ventricular (LV)
The condition is characterized by the presence of noncaseat- dysfunction [13].
ing granulomas. The most frequently involved organs include While sarcoidosis can affect any part of the heart and remain
the lungs, lymphatic nodes, skin, and eye. Half of patients with absolutely asymptomatic, it can also manifest itself as severe
the most frequent form of the condition – referred to as lung heart failure or arrhythmias resulting in sudden cardiac death;
sarcoidosis – remain asymptomatic, with only radiologically critical factors invariably include the extent and localization of
documented involvement of the hilar nodes. In the other half cardiac tissue involvement and disease activity [2,14].
of patients, lung parenchyma is also involved and patients
present with cough, exertional dyspnea and low-grade fever
Clinical manifestations
[1]. Active granulomatous inflammation may progress to
tissue fibrosis [2]. Besides the lungs, sarcoidosis may affect
any other organ system within the body. The prevalence of Complete heart block is the most common finding in patients
sarcoidosis is estimated at 10–20/100,000 persons [3]. However, with cardiac sarcoidosis (CS) and can be present in up to 30% of
the prevalence of sarcoidosis in some populations such as these patients [15]. However, lower degree atrioventricular
African Americans, Scandinavians or Japanese is markedly (AV) blocks as well as intraventricular conduction defects may
higher [4]. Women are affected more often than men. The also develop. From the pathophysiological point of view, the
disease most commonly develops between 25 and 45 years of conduction system becomes infiltrated by sarcoid granulomas.
age, with another peak occurring between ages 50 and 60 [4,5]. Ventricular arrhythmias are the second most common
Despite intensive research in this field, the etiology of the manifestation of CS. Triggered activity and abnormal auto-
condition remains unclear. It is most likely an exaggerated maticity secondary to inflammation can be present, though a
immunological response to an unknown antigenic stimulus. macroreentrant mechanism around areas of a granulomatous
To date, both infectious and environmental factors (pesticides, scar is more common [16]. Supraventricular arrhythmias are
aluminum, talc, etc.) have been implicated. An important role also frequent and are typically caused by atrial dilation
is believed to be played by genetic predisposition [6–8]. secondary to LV dysfunction or mitral regurgitation, although
infiltration of atria by granulomatous process can play a role in
Cardiac sarcoidosis some patients [15].
Extensive myocardial infiltration by granulomas may
Symptomatic involvement of the heart is relatively rare and deteriorate both systolic and diastolic LV function with the
reported to only occur in 2–5% of patients with pulmonary/ patient subsequently developing heart failure [17].
 cor et vasa 60 (2018) e155–e164
Valve dysfunction is a less frequent manifestation of CS.
The valve affected most often is the mitral valve, usually
associated with secondary mitral regurgitation in the presence
of LV dilatation and dysfunction. A role may also be played by
papillary muscle infiltration, with the valve itself affected
more rarely [17] resulting in severe regurgitation progressing
eventually to severe pulmonary hypertension or hemodynam-
ic instability.
While pericardial involvement is relatively frequent in CS,
progression to clinically manifested pericarditis or tamponade
is rare [15].
Cor pulmonale can be also present and is caused due to
right ventricular overload by pulmonary hypertension. Pul-
monary hypertension can develop either due to pulmonary
parenchyma injury or can have a postcapillary component in
the presence of LV dysfunction.
Diagnosis
Given the non-specific symptoms of cardiac sarcoidosis and
the fact that no single examination technique is currently
available to reliably detect cardiac sarcoidosis, its diagnosis is
usually quite challenging. The diagnosis is based on histologi-
cal verification of noncaseating granulomas in cardiac tissue
or, more often, in patients with biopsy-proven extracardiac
sarcoidosis, on the presence of typical abnormalities detected
by imaging techniques; however, invariably this diagnosis is
made only after ruling out all alternative diagnoses (Table 1).
There are several recommendations for the diagnosis of
cardiac sarcoidosis, with the best known being those pub-
lished by the Japanese Ministry of Health and Welfare [18] or
the World Association of Sarcoidosis and Other Granuloma-
tous Diseases (WASOG) [19]. However, the latest and most
useful recommendations for clinical practice are those
formulated in a Heart Rhythm Society (HRS) expert consensus
statement [20].
Electrocardiography (ECG), in addition to a careful personal
history and physical examination, should be performed on all
Table 1 – Diagnostic criteria of cardiac sarcoidosis – adapted from the Heart Rhythm Society expert consensus statement
[20].
1) Histological diagnosis – based on histological myocardial tissue sampling – presence of noncaseified granuloma without another plausible
cause
2) Clinical diagnosis – cardiac sarcoidosis is likely when:
a) diagnosis of extracardiac sarcoidosis has been documented by histology
and
b) one or more of the following criteria are present:
I. cardiomyopathy or AV block responsive to corticoid therapy or another type of immunosuppression
II. reduced LV ejection fraction (<40%) with no other explanation
III. unexplained sustained ventricular tachycardia
IV. AV block Mobitz II or third-degree AV block
V. positive PET
VI. LGE on CMR in typical localizations
VII. positive gallium scan
and
c) other potential causes of the above have been ruled out
AV, atrioventricular; CMR, cardiac magnetic resonance; LGE, late gadolinium enhancement; LV, left ventricle; PET, positron emission
tomography.
e157
patients suspected to have CS. While the sensitivity and
specificity of ECG in diagnosing sarcoidosis is low [21], it may
be helpful in identifying conduction disorders, increased
occurrence of premature ventricular beats, etc. Holter moni-
toring aids in detecting intermittent rhythm disturbances,
which are very often present among CS patients, and are
usually not identified by single ECG recordings.
Echocardiography itself does not have sufficient sensitivity
or specificity to establish the diagnosis of CS and is mostly
helpful in later stages of disease; however, it is often the first
examination suggesting cardiac sarcoidosis. Abnormalities
seen on transthoracic echocardiography include LV hypertro-
phy (Fig. 1), particular in basal segments of the myocardium,
impaired regional or global LV kinetics, impaired LV filling,
myocardial non-homogeneity (Fig. 2), mitral regurgitation,
pericardial effusion, pulmonary hypertension, and other
conditions. A typical but uncommon finding is thinning of
the basal interventricular septum [22]. While, in the initial
stages of disease, the most frequent findings include LV
diastolic dysfunction, later the echocardiographic picture may
mimic dilated cardiomyopathy, with a LV aneurysm occasion-
ally present [23,24].
Cardiac magnetic resonance (CMR) is currently the tech-
nique of choice in diagnosing cardiac sarcoidosis due to
excellent tissue contrast [10,25]. The CMR protocol should
contain a fast gradient cine sequences to evaluate morphology
and kinetics, a double-inversion T2-weighted sequence to
evaluate edematous changes, and finally, gradient inversion
recovery T1-weighted images in the late contrast-enhanced
phase (i.e. at least 7 min after gadolinium contrast agent
administration) are essential. In cases of an active inflamma-
tory process, focal myocardial thickening with impaired
kinetics and signal increase in T2-weighted images can be
observed. Such a finding corresponds to edema and granulo-
matous infiltration; furthermore, these patterns are usually
accompanied by the presence of late gadolinium enhance-
ment (LGE) that appears as hyperintense areas within the
myocardium with nulled signal [26]. The chronic fibrotic phase
of CS is characterized by the presence of linear and nodular
e158 cor et vasa 60 (2018) e155–e164

Fig. 2 – Transthoracic echocardiography, modified

Fig. 1 – Transthoracic echocardiography, apical 4-chamber
view; hypertrophy of basal interventricular septum with
slight hyperechogenicity in 38-year-old male patient with
known pulmonary sarcoidosis; no history of arterial
hypertension or valvular heart disease.
parasternal long-axis view; granulomatous infiltration
(arrows) of left ventricular posterior wall in 35-year-old
female patient with pulmonary and cardiac sarcoidosis.
IVS, interventricular septum; LA, left atrium; LV, left
ventricle; LVPW, left ventricular posterior wall; PM,
posteromedial papillary muscle.

LGE regions [2,27] that can theoretically occur in any cardiac

location, but are most often located in the mid-myocardial or
sub-epicardial layer of the left ventricular wall, the extent may
be even transmural in advanced cases. These patterns are
commonly observed in the basal septum (Figs. 3 and 4) and
lateral wall of the LV. In addition to presence of LGE, the fibrous
scar can lead to the wall thinning and impaired kinetics [27].
Studies investigating the usefulness of cardiac MR imaging for
diagnosis of CS report with sensitivity of 75% -100% and
specificity of 76.9%-78% [28]. In differential diagnosis, it is
usually possible to distinguish CS from post-ischemic changes
as these usually develop in the subendocardial layer and
respect the coronary artery territory; on the contrary, it is very
difficult to distinguish CS and myocarditis since both diseases
are inflammatory processes and their CMR appearance may
overlap, both in the acute and chronic stages [28]. In addition
to its diagnostic role, CMR is helpful in the risk stratification of
Fig. 3 – Contrast-enhanced magnetic resonance images in 4-
patients with CS. LGE has been shown to be a marker of a poor
chamber plane in 61-year-old male patient with bioptically
prognosis, particularly because of malignant arrhythmias and
proven pulmonary sarcoidosis showing mid-myocardial
sudden cardiac death [29]. Hence, LGE may serve as a factor in
linear region of LGE located in the basal septum
the decision-making regarding the implantation of implant-
(arrowhead) corresponding to the heart involvement.
able cardioverter-defibrillators (ICD) [20,30]. Other areas of
potential use of CMR include monitoring of disease activity
and response to therapy, although PET seems to be the
superior method here [31]. Distinct disadvantages of CMR
include its high costs and its still limited availability. However, ment. While single-photon emission computer tomography
the main limitation is the presence of contraindications (SPECT) using 99mtechnecium, 201thalium or 67gallium may be
including an implanted pacemaker or ICD (unless MRI- helpful in establishing the diagnosis and monitoring of
compatible), as a substantial number of patients with CS response to therapy, the technique – given its relatively low
require implantation of either of these devices. specificity and sensitivity – is being slowly abandoned in this
Nuclear medicine techniques present effective tools for indication to be replaced by positron emission tomography
assessing the extent of myocardial inflammatory involve- (PET) using 18F-fluorodeoxyglucose (FDG). PET is capable of
 cor et vasa 60 (2018) e155–e164
Fig. 4 – Contrast-enhanced magnetic resonance images in
short axis plane in 49-year-old male patient with
bioptically proven pulmonary sarcoidosisdisplaying
multiple mid-myocardial linear and nodular regions in the
ventricular septum (arrowheads) corresponding to cardiac
sarcoidosis.
visualizing active disease with sensitivity higher than that of
scintigraphy [10,20,25]. Its specificity has not been clearly
determined due to absence of a gold standard for diagnosing
CS. By displaying sites of excessive glucose metabolism in
areas of macrophage-mediated inflammation the FDG-PET
can identify early stages of CS before developing structural
alterations such as scaring or fibrosis [32]. Suppression of
physiologic cardiac FDG uptake using dietary modifications
(e.g. a high fat, high protein, low carbohydrates diet),
prolonged fasting (6–12 h prior to FDG administration),
intravenous heparin administration or their combinations is
vital [32–34]. Focal (or ‘‘focal on diffuse’’ pattern in patients
with suboptimal physiologic FDG suppression) uptake of FDG
is then a characteristic feature of CS. Again, most often are the
changes apparent in basal septum, inferolateral segment of LV
and in papillary muscles [33]. However, isolated augmented
uptake of FDG in the lateral wall of LV is often found in healthy
individuals and therefore is not considered as diagnostically
significant [32,33]. A combination of FDG-PET and rest
myocardial perfusion study using 13N-ammonia or 18rubidium
PET or 99mtechnecium scintigraphy is recommended for
diagnosing of CS [32–35]. FDG accumulation (‘‘hot spots’’) on
FDG-PET indicates inflammation, while perfusion defects
(‘‘cold spots’’) on PET or scnitigraphy perfusion scan identifies
areas of fibrosis [32,33]. The presence of both – perfusion defect
and FDG uptake – has the strongest association with death or
ventricular tachyarrhythmias [35]. Depending on the results of
these two tests, several classifications have been developed
[34–36]; we consider this one the most useful (modified from
[34]):
e159
Fig. 5 – 99mTc-MIBI SPECT (upper line) and FDG-PET scan
(bottom line) in 54-year-old female patient with cardiac
sarcoidosis. Visible perfusion defects in anteroapical
region and IVS of LV suggested of fibrosis. FDG uptake in
anteroapical region, IVS and inferior wall of LV
representing areas of active inflammation. FDG,
fluorodeoxyglucose; HLA, horizontal long axis; IVS,
interventricular septum; LV, left ventricle; MIBI,
methoxyisobutylisonitrile; PET, positron emission
tomography; SA, short axis; SPECT, single-photon
emission computer tomography; VLA, vertical long axis.
Courtesy of Prof. MUDr. Milan Kaminek, Ph.D., Department
of Nuclear Medicine, University Hospital Olomouc, Faculty
of Medicine and Dentistry, Palacky University, Olomouc,
Czech Republic.
no perfusion defect + no FDG uptake ! normal
no perfusion defect + focal FDG uptake ! early stage
(inflammation in absence of fibrosis)
mild to moderate perfusion defect + focal FDG upta-
ke ! progressive stage (Fig. 5)
severe perfusion defect + no FDG uptake ! late stage of CS
(fibrosis/scar)
The main disadvantages of PET include its higher costs,
lower availability and, in particular, radiation exposure.
However, unlike CMR, patients with an implanted device
(pacemaker or an ICD) can be examined. Moreover, PET is
capable of visualizing the activity of even extracardiac
involvement. Another potential advantage is the possibility
to use FDG-PET to monitor the response of the disease to
therapy [31], prospectively even by using quantitative assess-
ment of FDG uptake [32,34], although this assumption requires
further validation in prospective studies.
Although detecting non-caseating granulomas in myocar-
dium is considered the gold standard for diagnosis of CS,
endomyocardial biopsy (EMB) is usually not helpful. Despite its
high specificity, given a patchy myocardial involvement –
mostly in the basal segments of the left ventricle – yield of EMB
is usually low, with a sensitivity of 25% [37]; hence, EMB is not
routinely recommended. Its sensitivity can be enhanced by
electroanatomical mapping, CMR or PET [20,38]. In patients
with concomitant extracardiac forms of sarcoidosis, who
make an overwhelming majority of CS patients, the recom-
mendation is to perform lymphatic node or lung biopsy, with
EMB to be performed only in cases whereby extracardiac
e160 cor et vasa 60 (2018) e155–e164
biopsy is unfeasible [20]. Thus, EMB should be considered
mainly in patients with suspected isolated CS.
Diagnosis of CS is usually easier in patients with already
diagnosed extracardiac sarcoidosis, whereby any abnormality
documented by ECG, imaging techniques or symptoms such as
dyspnea, palpitations, or syncope, make the physician
consider involvement of the heart by sarcoidosis. Any patient
with known extracardiac sarcoidosis should have a detailed
clinical assessment focused on heart symptoms, 12-lead ECG,
at least 24-h Holter monitoring, and echocardiography. If no
abnormalities are documented by this panel of examinations,
the diagnosis of cardiac sarcoidosis is very unlikely and the
patients do not require any additional assessment as their
prognosis is very good. However, they do require regular
follow-up at least every 12 months as the disease may
progress. Still, should the screening examinations reveal
any pathology, further assessment is indicated, particularly
using CMR and PET [20] (Fig. 6).
The situation is more challenging in patients not yet
diagnosed to have sarcoidosis. Generally, cardiac sarcoidosis
should be considered in patients below age 60 in the presence of:
a) ‘‘idiopathic’’ third-degree AV block or Mobitz II AV block;
b) ventricular tachycardia that cannot be explained otherwise,
or in patients experiencing sudden cardiac death;
c) heart failure of unclear etiology.
It is especially the presence of idiopathic complete heart
block or Mobitz II AV block that should lead the physician to
Fig. 6 – Diagnostic algorithm in patients with diagnosed and
biopsy-verified extracardiac sarcoidosis – adapted from
[10,20]. CMR, cardiac magnetic resonance; PET, positron
emission tomography.
suspect cardiac sarcoidosis and initiate the diagnostic algo-
rithm shown below (Fig. 7). According to some studies [39,40],
in up to one third of these patients, the conduction disturbance
is actually caused by cardiac sarcoidosis.
As cardiac involvement in sarcoidosis is a marker of a grim
prognosis, early diagnosis and subsequent initiation of
therapy (medical and device) are crucial. It should likewise
be noted it is critical to search for extracardiac (especially
mediastinal and lung) involvement in cooperation with
pulmonologists, ophthalmologists, neurologists and other
specialists.
Treatment
Treatment of cardiac sarcoidosis includes both treatment of
the underlying disease (sarcoidosis per se) and that of sequels
of cardiac involvement (management of heart failure, pace-
maker or ICD implantation, etc.).
Given its unclear etiology and pathogenesis, no causal
treatment of sarcoidosis has been proposed to date. Treatment
is focused primarily on reducing inflammatory activity and
prevention of fibrosis, with the key role played by corticoids
[2,10,12,25,41], although data on their efficacy from random-
ized clinical trials are lacking. The dose of corticoids has
likewise not been defined yet. Generally, the starting dose
should be 40–60 mg of prednisone daily to be progressively
tapered to a maintenance dose of 10–15 mg daily or every other
day for 6–12 months [2,10,12,25,41]. Whenever reducing the
Fig. 7 – Diagnostic algorithm in patients without previously
diagnosed extracardiac sarcoidosis – adapted from [10,20].
AV, atrioventricular; CMR, cardiac magnetic resonance; EF,
ejection fraction; EMB, endomyocardial biopsy; HRCT,
high-resolution computed tomography; PET, positron
emission tomography.
 cor et vasa 60 (2018) e155–e164 e161

dose, usually by 5 mg every one or two months, the patient
should be closely monitored for disease activity. Corticosteroid
treatment should be continued for at least 12–24 months. In
the event of complete remission, it is possible to consider
withdrawing corticoids; however, with close monitoring of the
patient as the risk of relapse is up to 25% [2]. Corticosteroids are
usually effective in suppressing ventricular arrhythmias [42],
can be helpful in restoring AV conduction [43] and also
effectively improve LV function [44]. However, the effect of
corticoids in patients with LV ejection fraction (EF) <30%
seems to be minimal, which may be due to progression of
active inflammation to fibrosis no longer responsive to
immunosuppressive therapy [44]. In patients showing inade-
quate response to corticosteroids, use of other agents can be
considered such as methotrexate, azathioprine, mycopheno-
late mofetil, leflunomide, cyclosporine, or cyclophosphamide
[2,10,31,45,46]; however, the body of data regarding their
efficacy is even smaller. These corticosteroid-sparing agents
are mostly used in patients who require the maintenance dose
of prednisone >10 mg/day or who cannot tolerate side effects
of corticosteroids [47]. Dosing of selected corticosteroid-
sparing agents is shown in Table 2. The role of tumor necrosis
factor alpha inhibitors in treatment of CS remains controver-
sial. Their efficacy in CS has been reported in small case series
[48]. On the other hand, these agents can worsen heart failure
in non-sarcoidosis patients and have potentially serious side
effects. They can be considered as third-line agents in selected
patients [47]. Treatment, its initiation, dosing schedule and,
most importantly, its discontinuation, should be invariably
Table 2 – Maintenance doses of selected corticosteroid-
sparing agents in patients with cardiac sarcoidosis.
Methotrexate 10–20 mg/week
Azathioprine 50–200 mg/day
Hydroxychloroquine 200–400 mg/day
Leflunomide 10–20 mg/day
consulted within a multidisciplinary team, including at least
pulmonologists and, should other organs be also involved,
with experts in the respective specialties.
Medical therapy of heart failure in patients with cardiac
sarcoidosis is not different from that of patients with heart
failure of another etiology. Only in patients without an
implanted pacemaker or ICD beta-blockers should be started
with caution because of frequent AV conduction disorders.
As mentioned above, treatment of cardiac sarcoidosis
patients includes implantation of permanent pacemakers or
ICDs. The indications for pacemaker implantation in patients
with cardiac sarcoidosis do not differ from those applicable to
the general population [20,49,50]. The recommendation is to
consider pacemaker implantation also in cases where AV
block has temporarily resolved [20,50] so sarcoidosis should
not be perceived as a completely reversible cause of AV block.
To explain, corticoid therapy does not always result in
complete restoration of AV conduction so AV blocks may
recur and pose a potential life-threatening condition. Indica-
tions to cardiac resynchronization therapy do not differ from
the general indication criteria [20,49,50].
As cardiac sarcoidosis patients are at risk of increased
incidence of malignant arrhythmias and sudden cardiac
death, modified criteria were proposed for ICD implantation
in these patients. Use of ICDs in secondary prevention in these
patients, i.e., in patients surviving sudden cardiac death or
those documented to have sustained ventricular tachycardia,
is a straightforward indication [20,49,50]. In primary preven-
tion, ICD implantation should be considered – in addition to
general indications for ICD implantation – in patients with
previous syncope believed to have an arrhythmogenic cause
[20]. Some authors have suggested the consideration of ICD
implantation in all sarcoidosis patients indicated for pace-
maker implantation [20,51]. Furthermore, ICD implantation
can be considered in patients with an LV EF of 36–49% and/or
right ventricular EF <40% despite optimal medical therapy
(waiting period of at least 3 months) [20], especially in those

Table 3 – Recommendations for ICD implantation in cardiac sarcoidosis patients – adapted from the Heart Rhythm Society
expert consensus statement [20].
Class I ICD implantation is recommended in patients meeting at least one of the following criteria:
1) Sustained ventricular tachycardia, including prior cardiac arrest
2) LV EF ≤35% despite optimal medical therapy and immunosuppression (in the presence of active inflammation)

Class IIa ICD implantation can be useful in patients, regardless of their LV function, meeting at least one of the following criteria:
1) Indication for permanent pacemaker implantation
2) Status after syncope or pre-syncope likely to be of arrhythmogenic etiology
3) Inducible sustained ventricular tachycardia (whether monomorphic or polymorphic) or clinically
relevant ventricular fibrillation

Class IIb ICD implantation may be considered in patients with LV EF 36–49% and/or right ventricular EF <40%
despite optimal medical therapy and immunosuppression (in the presence of active inflammation)

Class III ICD implantation is not recommended in patients without a history of syncope, with normal LV and
right ventricular EF, absence of LGE on CMR, with negative electrophysiology study, and no indication
for permanent pacing. Nonetheless, these patients should be closely monitored for their LV and right ventricular function
ICD implantation is not recommended in patients meeting at least one of the following criteria:
1) Incessant ventricular tachycardias
2) Severe NYHA class IV heart failure
CMR, cardiac magnetic resonance; EF, ejection fraction; ICD, implantable cardioverter/defibrillator; LGE, late gadolinium enhancement; LV, left
ventricular; NYHA, New York Heart Association.
e162 cor et vasa 60 (2018) e155–e164
with a positive electrophysiology study [20,52] or in patients
with extensive myocardial involvement documented by CMR
(or alternatively by PET) [20,30]. The indication criteria
developed by HRS are shown in Table 3.
Medical therapy of arrhythmias in cardiac sarcoidosis is
challenging. While beta-blockers tend to further increase the
already high risk of AV conduction disorders, and amiodarone
will potentially worsen lung involvement [41], either can be
used with caution [20] – both in ventricular and supraventric-
ular arrhythmias. Drugs contraindicated in cardiac sarcoidosis
include Class I antiarrhythmics given their potential proar-
rhythmogenic effect in myocardial injury [20].
Radiofrequency ablation (RFA) to modulate the substrate of
malignant arrhythmia should be considered in patients with
ventricular arrhythmias despite corticosteroids and antiar-
rhythmic therapy (amiodarone, sotalol) [20,53]. In patients
showing, in particular, involvement of the epicardial layers of
the myocardium, the epicardial approach is often imperative
to successfully terminate the arrhythmia [10]. Nonetheless, in
patients with extensive involvement and development of
appreciable myocardial fibrosis, the outcome of RFA is
uncertain [54].
The last resort in the treatment of cardiac sarcoidosis
unresponsive to standard therapy is heart transplantation.
Quite surprisingly, the 1- and 5-year survival rates of
transplant recipients for cardiac sarcoidosis are superior to
those of patients receiving grafts for other indications [55].
While graft involvement with sarcoidosis has been reported,
its incidence is unknown [56].
Conclusion
Cardiac sarcoidosis is a relatively rare condition which,
however, affects up 25% of patients presenting with extra-
cardiac sarcoidosis and is associated with a grim prognosis,
especially if symptomatic. As cardiac sarcoidosis affects mostly
younger patients with sudden cardiac death often being its first
manifestation, early diagnosis and initiation of therapy (both
medical and device) are absolutely crucial. A key role is played
particularly by screening of patients already diagnosed with
extracardiac sarcoidosis (assessment of symptoms, physical
examination, ECG, Holter monitoring, echocardiography),
which should be repeated at least every 12 months. Definitive
diagnosis is based on results of cMRI and PET. While a
dominant role in treatment is played by corticoids, patients
not infrequently receive pacemakers and ICDs. Of crucial
importance in the management of cardiac sarcoidosis patients
is interdisciplinary collaboration of cardiologists, pulmonolo-
gists, radiologists, and other specialists.
Conflict of interest
None declared.
Ethical statement
The research was done according to all ethical standards.
Funding body
None.
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