Etiology ; Genetic predisposition → Unknown stimuli trigger an exaggerated immune response → Noncaseating granulomas

Clinical manifestations ; The clinical manifestations vary from asymptomatic to heart failure, AV conduction block and sudden death.

Sudden cardiac death ; One quarter of patients with sarcoidosis have cardiac lesions, but there is a poor correlation between symptoms and myocardial involvement even in the most advanced cases, and hence SCD may be the first manifestation. (Mitchell DN, du Bois RM, Oldershaw PJ. Cardiac sarcoidosis. BMJ 1997;314:320-1.)

Holter monitor ; Supraventricular and ventricular arrhythmias occur frequently (73%), bundle-branch block is present in about two thirds of patients. Approximately one quarter of these patients develop complete heart block. Holter monitor can be useful for the identification of rhythm disturbances. (Mitchell DN, du Bois RM, Oldershaw PJ. Cardiac sarcoidosis. BMJ 1997;314:320-1.)

AV block ; Kandolin et al adopted a protocol to collect up to 12 biopsy samples under echo guidance. Of 72 patients with unexplained AV block they diagnosed CS in 14 (19%) and 9 of those had isolated CS. (Kandolin R, Lehtonen J, Kupari M, Cardiac sarcoidosis and giant cell myocarditis as causes of atrioventricular block in young and middle-aged adults, Circ. Arrhythm. Electrophysiol. 2011;4: 303–309.)

Biomarkers ; Biomarkers and markers of systemic inflammation are less useful in isolated CS. There appears to be a role for high sensitivity troponins and BNP in diagnosis and activity monitoring in CS but their value requires further validation. (Isobe M, Tezuka D, Isolated cardiac sarcoidosis: Clinical characteristics, diagnosis and treatment. International Journal of Cardiology 2015;182: 132–140.)

Diagnose in the presence of extracardiac disease ; The JSSOG adopted the algorithm to diagnose CS in the presence of extracardiac disease by two major clinical and imaging criteria → Major criterias; Advanced AVB or sustained VT, LVEF < 50% or wall thinning, FGS uptake on PET, +DGE on CMR, Granuloma on biopsy.

It is important to note that many patients with extracardiac sarcoidosis have an asympthomatic cardiac involvement while other have a minor involvement which does not satisfy the above criteria. For example, in the study by Nagao et al of 274 patients diagnosed with extracardiac sarcoidosis 47 had cardiac involvement in the course of the first year of follow up. Among the remaining 227 with no cardiac manifestations, 25% still had ECG abnormalities and those were associated a markedly increased event rate (23.8 vs 1.5 per 1000 person*years). (Nagao S, ... , Minamino T. Electrocardiographic abnormalities and risk of developing cardiac events in extracardiac sarcoidosis. Int J Cardiol. 2015;189:1-5.)

Diagnosing isolated CS ; The algorythm for diagnosing isolated CS requires high index of suspicion, ruling out coronary artery disease, other forms of myocarditis and then searching for systemic granulomatuous disease. (Isobe M, Tezuka D, Isolated cardiac sarcoidosis: Clinical characteristics, diagnosis and treatment. International Journal of Cardiology 2015;182: 132–140.)

While endomyocardial biopsy remains a gold standard, certain imaging results (such as interventricular septal wall thinning to less than 4 mm) are highly specific to cardiac sarcoidosis.

Immunosuppressive therapy ; CS is an indication for immunosuppressive therapy although the threshold for initiating therapy for minor cardiac abnormalities is not established.

Most experts start with Prednisone 40-60 mg/day and attempt to taper down to 10 mg/day and below within 6-12 months. There is no concensus how to use immunomodulators for steroid sparing and whether/when to discontinue completely the steroids. There are no established guidelines how to monitor the disease activity in the heart during tapering and discontinuation of therapy.

ICD & Pacemaker ; By using corticosteroid the danger of SCD may also be diminished and an improvement may also be seen in conduction defects. The use of immunosuppression by no means eliminates the risk of further occurrence of arrhythmias. Prospective trial data do not exist, but spontaneous VT, severe LV dysfunction, and severe intraventricular conduction disturbance warrant ICD and/or pacemaker therapy as appropriate. (Fleming HA, Bailey SM. Sarcoid heart disease. J R Coll Physicians Lond 1981;15:245–53.)

While many are eager for primary prevention ICD in patients with CS, there is no concensus on this topic. There is a consensus on implanting a device in CS with LVEF = 35% despite optimal medical therapy.

CARDIAC SARCOIDOSIS: EPIDEMIOLOGY, CHARACTERISTICS, AND OUTCOME OVER 25 YEARS IN A NATIONWIDE STUDY

Kandolin R,..., Kupari M. Cardiac sarcoidosis: epidemiology, characteristics, and outcome over 25 years in a nationwide study. Circulation. 2015 Feb 17;131(7):624-32.

This study was designed to assess the epidemiology, characteristics, and outcome of cardiac sarcoidosis (CS) in Finland. The authors collected data on all cases of histologically confirmed CS in Finland over the last 25 years focusing on the epidemiology, characteristics, and long-term outcome of CS. 110 cases were included (51±9, 27-69 yr., 65% females).

• The initial cardiac manifestation was AV block in 44%, VT/VF in 33% and heart failure in 18%.

• On ECG 45% had advanced AV block, 37% had RBBB and 21% - LBBB.

• Left ventricular systolic dysfunction was found in 59% and delayed gadolinium enhancement on CMR was found in 83%; these were more common in isolated CS. Abnormal myocardial uptake of FDG was found in ~70% (FDG-PET).

• Elevated serum ACE, lysozyme and hypercalciuria were found in ~50% and these were relatively uncommon in individuals with isolated CS.

Steroids were given to 102/110 and other immunosuppressors (mostly azathioprime) to 62. Steroids went uninterrupted in 48, were given intermittently in 54 but had to be discontinued in 4 patients. This paper does not specify if there were differences in outcome between patients who were on permanent steroids compared to those who discontinued.

ICD was impanted in 59% and permanent pacemaker in another 29%. On median follow up of 79 (12-303) months, 10 experienced a cardiac death (9 sudden) and 11 underwent heart transplantation. Another 11 had ventricular fibrillation as their first cardiac event: either aborted sudden death (n=8) or an appropriate ICD shock for VF (n=3).

 

Compilation by Dr. Samad Ali Moradi; ESC 01 JUN 2015 Paper, Also according to author's work experience and guidelines.