Although there is a broad differential diagnosis for the presenting symptoms of CS, in young patients without ischemic heart disease, the likelihood of underlying CS increases. Accordingly, patients without previously known systemic sarcoidosis should be queried for history suggestive of multisystem involvement (e.g. cough, iritis, dermatologic abnormalities). Here, the identification of non-cardiac involvement and establishment of diagnosis through histologic evaluation (e.g. lymph node biopsy) can be pivotal.

The diagnosis of sarcoidosis limited to the heart without extra-cardiac features is challenging. The classic teaching is that isolated CS is rare, however the epidemiologic data are suspect. Anecdotal experience includes patients only recognized to have CS at the time of cardiac transplantation, when the explant is carefully examined by a pathologist, or at autopsy. Our general approach is to extensively evaluate for CS in young patients presenting with infrahissian block, dilated cardiomyopathy with conduction disease and/or arrhythmia, or repetitive multifocal monomorphic VT.

A relatively high prevalence of CS has been reported in adult patients younger than 60 presenting with AV block [4]. In a single center prospective study utilizing FDG-PET in 32 young and middle aged adults presenting with idiopathic AV block, CS was identified in 34 % of subjects. All were subsequently found to have systemic sarcoidosis. In addition to ischemic heart disease, Lyme carditis and inherited neuromuscular disease should be considered alongside CS in these patients.

In patients without ischemic heart disease who present with sustained VT, cardiac sarcoidosis may be present in up to 10 % of cases [5, 6]. These patients are usually middle aged with multifocal monomorphic VT and electrophysiological evidence of scar reentry. Left ventricular systolic dysfunction and AV block often, but not universally, coexist with VT in these patients.

Dilated cardiomyopathy with conduction disease and/or arrhythmia (DCM+E) has been variably described in the literature as conduction cardiomyopathy [7], DCM+E [8] or arrhythmogenic cardiomyopathy [9]. By recognizing a heavy burden of conduction disease and/or arrhythmia in DCM, the differential diagnosis can be narrowed to a number of etiologies with specific therapeutic and prognostic implications [8]. Broadly categorized, DCM+E can be caused by ischemic, genetic, infections, and inflammatory etiologies. Once ischemic heart disease has been excluded, key clinical features can be used to distinguish amongst the other pathologies and definitive testing is often available.

A family history of unexplained sudden death, heart failure or cardiac transplantation should be obtained. Genetic testing, inclusive of genes commonly mutated in DCM+E (LMNA, DES, SCN5A, EMD, DSP, PKP2, DSC2), is now widely available. Although results will not be available for up to 14 weeks, the identification of a disease causing DNA variant in the appropriate clinical context can provide definitive diagnostic information allowing the reasonable exclusion of alternate etiologies including CS along with the identification of at risk family members [10, 11].

Residence or extended travel to areas where infection with Trypanosoma cruzi is endemic is key to identifying patients with Chagas heart disease [12]. Like CS, Chagas heart disease can present with conduction disease, regional wall motion abnormalities and ventricular tachyarrhythmia. Serologic testing in the appropriate setting can identify patients with Chagas heart disease and can enable therapy with anti-parasitic therapies such as benznidazole which may alter the natural history of this otherwise unrelenting disease [13]. Moreover, erroneous use of immunosuppression for presumed CS in a patient with Chagas heart disease could lead to accelerated pathogenesis [14].

Giant cell myocarditis (GCM) is a rare but devastating inflammatory cardiomyopathy with many of the same clinical features of CS, albeit with a rapidly progressive course. Amongst patients presenting with rapidly progressive cardiomyopathy, often without dilated remodeling, GCM should be considered. Although therapy for giant cell myocarditis is unrefined, its identification should prompt consideration for cardiac transplantation owing to its generally poor prognosis. Unlike CS where the yield of endomyocardial biopsy is generally low (see Chap.​ 9) the diffuse myocardial involvement in GCM is usually readily apparent on biopsy.

Our approach to the evaluation of sarcoidosis is context dependent, as enumerated above. In patients with proven systemic disease, the exclusion of coronary heart disease and either FDG-PET or CMR findings suggestive of CS are usually sufficient to make a diagnosis. However, we prioritize this testing to precede ICD implantation or radiofrequency ablation due to the limiting/confounding effects of these therapies on non-invasive testing. Amongst patients with suspected isolated CS, we perform a thorough evaluation for extra-cardiac sarcoidosis, enhanced with FDG-PET. If not present, we have a low threshold to perform endomyocardial biopsy. In this setting, the performance of voltage guided biopsy may increase the diagnostic yield and is generally favored [15, 16]. As noted earlier, the implantation of a PPM or ICD usually limits the performance of biopsy for at least a month due to concerns of lead dislodgement.

Medical therapy initiated in the acute care setting should be undertaken based on the severity of cardiac involvement and with a broader perspective of the patient’s multisystem involvement, prior therapies, and clinical trajectory. The response to prior immunosuppressive therapy, including corticosteroids and the use of steroid sparing agents is an important consideration. The presence of severe extra-cardiac disease may justify immunosuppressive therapy ipso facto. To the contrary, patients with advanced or end-stage cardiac involvement may have little to gain from immunosuppression and may only suffer its adverse consequences.

The content below focuses on the use of corticosteroid immunosuppression and presupposes that conventional therapies for heart failure (diuretics, neuro-hormonal antagonists) and arrhythmia (antiarrhythmic drugs, radiofrequency ablation) are used. In general, a diagnosis of CS should lead to the addition of immunosuppressive medications on top of conventional therapies.

As described in detail in Chap.​ 11, immunosuppressive therapies are frequently utilized in CS, albeit without prospective or well-designed clinical studies to inform dose, duration or extent of efficacy. The published studies likely reflect some degree of publication and ascertainment bias and usually only describe an individual center’s approach to management. Indeed the limitations of the published literature were highlighted in a recently published systemic review of the literature by Nery and colleagues [17]. They concluded that the best data exist for the efficacy of steroids for the management of AV block related to sarcoidosis and that the existing literature pertaining to VT and heart failure do not enable a statement of efficacy.

Of the different immunosuppressive agents used in sarcoidosis, the experience is greatest with corticosteroids. Because corticosteroids have a rapid onset of action, they are generally the agent used in the acute setting where rapid control of inflammation is desired. Steroid sparing agents such as methotrexate typically require weeks to take effect and accordingly are not reviewed here.