Evaluation of Cytokine Levels in Cardiac Transthyretin and Immunoglobulin Light Chain Amyloidosis and Their Correlation with Myocardial Inflammatory Cells and MACE

<b>Aims:</b> Myocardial inflammation in cardiac amyloidosis is associated with poor clinical outcomes. This study aimed to (a) investigate the relationship between peripheral blood cytokine levels and the presence of inflammatory cells within the myocardium, and to (b) evaluate the potential of cytokines as predictors of major adverse cardiovascular events (MACE) in transthyretin (ATTR) and immunoglobulin light chain (AL) cardiac amyloidosis. <b>Methods:</b> Peripheral blood samples were collected from 50 patients with cardiac ATTR or AL amyloidosis between 2018 and 2023 at baseline and every three months during follow-up visits. Cytokine analysis was performed using Olink's Proximity Extension Assay. For MACE prediction analysis, only patients with MACE occurring within ±14 days of a study visit were included (<i>n</i> = 16). Associations were evaluated using linear models. <b>Results:</b> No significant associations were identified between the EMB-confirmed myocardial presence of inflammatory cells and cytokine levels. There was a trend of weak-to-moderate associations between serial blood cytokine levels and MACE, albeit this was non-significant after adjustment for multiple testing (FDR): r² = 0.28 for PON3 (<i>p</i> = 0.00075, FDR = 0.28), SIGLEC1 (<i>p</i> = 0.00077, FDR = 0.28), and IL-6 (<i>p</i> = 0.00086, FDR = 0.31). <b>Conclusions:</b> Peripheral blood cytokine levels were not reliable biomarkers for the myocardial presence of inflammatory cells. PON3, SIGLEC1, and IL-6 demonstrated a statistically non-significant trend of a weak-to-moderate association with MACE in cardiac amyloidosis. Since we recently demonstrated that amyloidosis with an inflammatory component is associated with poor outcomes, these additional findings underscore the need for alternative approaches to identify and manage inflammation in this patient population.