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

<b>Background/Objectives:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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, <i>p</i> = 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, <i>p</i> = 0.04) and with higher ECV values (β = 0.008 per 1 pg/mL, <i>p</i> = 0.001). Regression analysis showed that aldosterone is associated with ECV (b-0.009, CI: 0.002-0.016, <i>p</i> = 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. <b>Conclusions:</b> 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.