Unmasking Early Cardiac Fibrosis in Sarcoidosis: The Role of Plasma Aldosterone and Cardiac MRI.

Background/Objectives: Cardiac sarcoidosis (CS) is a challenging diagnosis due to its subclinical progression and the limitations of existing screening tools. Cardiac magnetic resonance (CMR) and PET/CT imaging have improved diagnosis and detection. Aldosterone, a hormone with known profibrotic effects, may offer additional diagnostic value. We therefore aimed to determine whether plasma aldosterone level is associated with myocardial fibrosis, independent of active inflammation, in CS. Methods: This observational study included 541 patients with biopsy-proven sarcoidosis and preserved left ventricular ejection fraction (LVEF ≥ 50%). All underwent CMR with extracellular volume (ECV) mapping and 18F-FDG PET/CT to assess myocardial fibrosis and inflammation, respectively. Plasma aldosterone levels were also measured. Results: Plasma aldosterone levels were significantly higher in patients with cardiac sarcoidosis (172 [IQR 106-235] pg/mL) compared to those without cardiac involvement (143 [100-205] pg/mL, p = 0.02). Aldosterone was independently associated with the presence of late gadolinium enhancement (LGE) on CMR (OR 1.002 per 1 pg/mL increase; 95% CI 1.001-1.004, p = 0.04) and with higher ECV values (β = 0.008 per 1 pg/mL, p = 0.001). Regression analysis showed that aldosterone is associated with ECV (b-0.009, CI: 0.002-0.016, p = 0.009) and there was no interaction according to LGE status indicating a relationship with diffuse myocardial fibrosis even in the absence of visible scarring. No association was observed with T1-, T2-, or PET/CT-defined inflammation. Conclusions: Plasma aldosterone is a robust marker of myocardial fibrosis in sarcoidosis, particularly in early or subclinical stages. Its correlation with ECV-but not with inflammatory imaging markers-suggests its link with myocardial diffuse fibrotic remodeling before, and independently of, overt scarring or inflammation.