Pathophysiological Gaps, Diagnostic Challenges, and Uncertainties in Cardiac Sarcoidosis

Figures

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  Figure 1. Current knowledge gaps in cardiac sarcoidosis. A, Is there a definite diagnostic algorithm for CS? (B) Is there an isolated CS phenotype? (C) Is the cardiac noncaseating granulomatous inflammation a unique feature of cardiac sarcoidosis? (D) Is there a genetic background that predisposes to CS? (E) How can the treatment of CS be directed? (F) Which models are useful to study CS? ARVC indicates arrhythmogenic right ventricular cardiomyopathy; CS, cardiac sarcoidosis; DCM, dilated cardiomyopathy; and HCM, hypertrophic cardiomyopathy.

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  Figure 2. Examples of diagnostic findings in patients with CS. Fulfillment of current diagnostic criteria may vary because of different points in time of presentation (subclinical, active, quiescent, or burned‐out disease). All of the following findings are associated with patients with cardiac sarcoidosis and positive endomyocardial biopsy. Upper row (left to right): incomplete right bundle branch block, right bundle branch block, atrioventricular block III, and ventricular tachycardia. Middle row (left to right): no FDG uptake in PET‐CT and no late gadolinium enhancement in CMR, no FDG uptake in PET‐CT and late gadolinium enhancement in CMR, FDG uptake in PET‐CT and no late gadolinium enhancement in CMR, and FDG uptake in PET‐CT and late gadolinium enhancement in CMR. Bottom row (left to right): normal finding (sampling error), CD3+ T lymphocytes in lymphocytic myocarditis, CD3+ lymphocytes in noncaseating granuloma, and isolated CD3+ T lymphocytes and fibrosis; all images ×200. CMR indicates cardiovascular magnetic resonance; CS, cardiac sarcoidosis; EMB, endomyocardial biopsy; FDG, F18‐fluorodeoxyglucose; and PET‐CT, positron‐emission tomography‐computed tomography.

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  Figure 3. General proposed concept of granuloma formation in sarcoidosis. (1) Presentation of an unknown antigen by dendritic cells and macrophages to lymphocytes. (2) Recruitment of naive T cells and conversion to T helper 1 cells is followed by lymphocytic infiltration, accumulation of dendritic cells and macrophages caused by cytokines (ie, interleukin (IL‐2) and interferon‐γ. (3) M1 macrophages turn into epithelioid cells, epithelioid cells fuse to form multinucleated giant cells, granuloma formation including activated M1 macrophages, multinucleated giant cells, CD4+ helper T cells, and CD8+ cytotoxic T cells. (4) Transition from Th1 to Th2 predominance, induction of M2 macrophages, M2 macrophages potentially produce cytokine signals that stimulate fibrosis.